Analysis of the gut microbiome during pregnancy in T1D (Alpha and beta diversity analyses)
Alexandra Roth Schulze
2021-03-18
1 Background
This report shows the analysis performed for metagenomics sequencing from the gut microbiome of 66 pregnant women. For each pregnant woman, samples were taken at 1 to 3 different time points during the pregnancy (i.e. corresponding to trimesters, up until day ~280 when the child is born) to give a total of 134 samples. From the 66 pregnant women, XXX are diabetic (T1D). For some analyses, time points were categorised into trimesters, correspondence being:
Trimester 1 = 0-99 days Trimester 2 = 100-196 days Trimester 3 = 196-280 days
2 Background
This report shows the analysis performed for metagenomics sequencing from the gut microbiome of 70 pregnancies (36 in women with T1D) from a total of 66 different women. For each pregnant woman, samples were taken at 1 to 3 different time points during the pregnancy (i.e. corresponding to trimesters, up until day ~280 when the child is born) to give a total of 134 samples. From the 32 pregnant women, 16 are diabetic (T1D). For some analyses, time points were categorised into trimesters, correspondence being:
Trimester 1 = 0-99 days Trimester 2 = 100-196 days Trimester 3 = 196-280 days
3 Data generation
Samples were shotgun sequenced using the NovaSeq 6000 illumina sequencing machine at the Ramaciotti Centre for Genomics located at the University of New South Wales (UNSW) in Sydney, Australia.
3.1 Processing the sequences: from sequence data to feature table
The data was processed through pipelines developed by the group of Curtis Huttenhower at Harvard Univerisity and Broad Institute. These pipelines belong to the BioBakery.
The raw data was uploaded to the short read archive (SRA) database (https://www.ncbi.nlm.nih.gov/sra/) with accession number PRJNA604850.
KneadData (https://bitbucket.org/biobakery/biobakery/wiki/kneaddata) was used to filter human (“contaminant”) sequences as well as quality controlling the sequences This has to be done for each sample. Example:
kneaddata –input 4_S1_R1_001.fastq.gz –input 4_S1_R2_001.fastq.gz -db /home/users/allstaff/schulze.a/bin/Kneaddata/Homo_sapiens –trimmomatic /usr/local/bioinfsoftware/trimmomatic/trimmomatic-0.36 –output ./kneaddata_output -t 12HUMAnN2 (https://bitbucket.org/biobakery/humann2/wiki/Home) was employed to quantify gene families and pathways; and within HUMANn2, Metaphlan was also used to obtain taxonomic profiles. This process is also performed per sample and read pair1 and read pair2 need to be concatenated and saved in the same file prior to running HUMAn2 (i.e. end-pairing relationships are currently not taken into account during HUMAnN2’s alignment steps. This is due to the fact that HUMAnN2 strictly aligns reads to isolated coding sequences: either at the nucleotide level or through translated search. As such, it will frequently be the case that one read (READ1) will map inside a given coding sequence while its mate-pair (READ2) will not [information obtained from the manual]). Example of running HUMAnN2 with a sample:
humann2 -i NGU5366A1.fastq -o ./Output_HUMAnN2 –threads 28Running this outputs several files, among those is “NGU5366A1_metaphlan_bugs_list.tsv”, which is a list of the bacterial taxa found in that sample at all taxonomic levels (i.e. stratified data) and their relative normalizaed abundances. The script merge_metaphlan_tables.py was used to merge the MetaPhlAn output from several samples into one table taxa (rows) vs samples (columns) with the table enlisting the relative normalized abundances per sample per taxa. Example:
merge_metaphlan_tables.py metaphlan_output1.txt metaphlan_output2.txt metaphlan_output3.txt > ./merged_abundance_table_Rel_Abundance.txtAs mentioned above, the abundance table (profile) contains the stratified data. In order to obtain a table that contains the taxa at a specific taxonomic level (e.g. Species), grep was used. Example for species taxonomic level:
grep ’s__’ merged_abundance_table_Rel_Abundance.txt | grep -v ’t’ > merged_abundance_table_Rel_Abundance_Sp.tsv # -v (exclude) ’t’ will prevent from selecting those lines that have species and strain (’t__’) classification. We just need species in this case.Example for genus taxonomic level:
grep ’g__’ merged_abundance_table_Rel_Abundance.txt | grep -v ’t’ | grep -v ’s’ > merged_abundance_table_Rel_Abundance_Genus.tsvNote: For other taxonomic levels, this process was repeated for each taxonomic level.
This table contains the whole taxonomy for each taxa, from “kindom” to “Species” along with per sample abundances (i.e. counts per million [CPM]). From this table the taxonomy was obtained. The taxa table is then transformed into a biom file in JSON format and the taxonomic and metadata infomation were added with the software biom. Example:
biom convert -i merged_abundance_table_Rel_Abundance_Sp.tsv -o merged_abundance_table_Rel_Abundance_Sp.biom –table-type=“OTU table” –to-json
biom add-metadata –sc-separated taxonomy –observation-header OTUID,taxonomy –observation-metadata-fp Species_taxonomy.txt -i merged_abundance_table_Rel_Abundance_Sp.biom -o Pregnancy_NovaSeq_taxonomic_profile_Rel_Species_NV_wTax.biom
biom add-metadata -i Pregnancy_NovaSeq_taxonomic_profile_Rel_Species_NV_wTax.biom -o Pregnancy_NovaSeq_taxonomic_profile_Rel_Species_NV_wTaxMet.biom –sample-metadata-fp ./metadata.csvThis process was repeated at for each taxonomic level.
The resulting taxa tables (one for each taxonomic level) with taxonomies and metadata were imported into R to process with the Phyloseq (https://github.com/joey711/phyloseq) and other packages. The data were first de-identified (i.e. data relating to the identification of the donor was removed) and R objects were saved (i.e. A total of 6 taxonomic and 3 functional files were generated). Those R objects were used as inputs in the analysis performed in this document. These objects and other files used in this markdown can be found at https://github.com/PapenfussLab/RothSchulze_pregnancy-gut-microbiome-T1D and all the paths needs to be changed in this document in order to reproduce the analysis.
4 Bar plots taxonomy
5 Alpha diversity
5.1 Alpha diversity (T1D vs. non-T1D continuous time [Days])
Call:
geeglm(formula = Observed ~ t1dfactor * days_c + age_c + nullip +
bmi_c + HLA, data = DivCal_R_df, id = motherid, corstr = "exchangeable")
Coefficients:
Estimate Std.err Wald Pr(>|W|)
(Intercept) 96.81936 2.39884 1629.005 <2e-16 ***
t1dfactorT1D 2.08666 2.12628 0.963 0.3264
days_c -0.01196 0.01817 0.433 0.5106
age_c -0.66073 0.27302 5.857 0.0155 *
nullipYes -4.17930 2.37889 3.086 0.0789 .
bmi_c -0.14664 0.20923 0.491 0.4834
HLADRXX -3.12808 2.91574 1.151 0.2833
HLAGroup3o4 -4.01888 2.66817 2.269 0.1320
t1dfactorT1D:days_c -0.02969 0.02971 0.998 0.3177
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
Correlation structure = exchangeable
Estimated Scale Parameters:
Estimate Std.err
(Intercept) 134.1 20.13
Link = identity
Estimated Correlation Parameters:
Estimate Std.err
alpha 0.2475 0.1093
Number of clusters: 121 Maximum cluster size: 3 5.2 Alpha diversity (time continuous [see T1D vs. non-T1D])
Call:
geeglm(formula = Observed ~ t1dfactor * Tri + age_c + nullip +
bmi_c + HLA, data = DivCal_R_df, id = motherid, corstr = "exchangeable")
Coefficients:
Estimate Std.err Wald Pr(>|W|)
(Intercept) 98.423 3.460 809.34 <2e-16 ***
t1dfactorT1D 4.508 4.165 1.17 0.279
TriT2 -1.151 3.170 0.13 0.717
TriT3 -1.690 3.183 0.28 0.596
age_c -0.676 0.270 6.25 0.012 *
nullipYes -4.315 2.350 3.37 0.066 .
bmi_c -0.180 0.213 0.71 0.399
HLADRXX -3.501 3.012 1.35 0.245
HLAGroup3o4 -4.497 2.766 2.64 0.104
t1dfactorT1D:TriT2 -0.614 5.047 0.01 0.903
t1dfactorT1D:TriT3 -4.127 5.140 0.64 0.422
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
Correlation structure = exchangeable
Estimated Scale Parameters:
Estimate Std.err
(Intercept) 135 20
Link = identity
Estimated Correlation Parameters:
Estimate Std.err
alpha 0.258 0.127
Number of clusters: 121 Maximum cluster size: 3 
6 Species taxonomic level
6.1 Microbial community composition analysis at Species level (Beta diversity analysi)
Hypothesis
Hypothesis: the gut microbiome taxonomic composition (i.e. Beta diversity) during pregnancy differs between women with and without T1D. In order to test if this hypothesis holds true, a measurement of the distance between each pair of samples is calculated (i.e. Bray-Curtis) and a repeated measure aware permutational analysis of variance (i.e. RMA-PERMANOVA) test is applied. A P-value <0.05 is considered to be significant, meaning that our hypothesis cannot be rejected. Borderline P-values are also considered positive.
Problems with the available R function for Beta diversity analysis
The current available function for performing hypothesis testing of differences in the microbiome composition between groups of samples is called Adonis (i.e. which perform a PERMANOVA test) and is part of the Rpackage vegan (Oksanen, J. et al). The main problem with this function is that if the metadata of interest does not vary with time (e.g. disease status, sex, etc.), adonis does not calculate the corresponding P value correctly, as it permutes levels within a subject. This does not make sense for something like disease status or sex as permuting within-subject will produce the exact same distribution each time you permute. This a known drawback of the adonis function for repeated measures.
In order to get the correct P-value for a time-invariant metadata, the permutation procedure has to be altered such that it permutes the subjects rather than levels within subjects, which apply to our current pregnancy dataset.
Here I'm running a script written by Jason Lloyd-Price from Curtis Huttenhower lab in Harvard. This script is being used instead of the regular Adonis (PERMANOVA test) from the R package Vegan because as stated above, our metadata of interest (i.e. T1D status) does not vary with time, we have a mixture of data which changes within and between an individual and we also have unequal group sizes (i.e. we do not always have exactly 3 samples per woman). For those three reasons, it was recommended to use his script to perform the RMA-PERMANOVA analysis.
PARAMETERS:
permute_within: This data frame has samples on rows and metadata on columns. This should only contain metadata that varies within a block (i.e. it's a single-column data frame with only time/Days).Since, the other metadata within the block should be the same between repeated measurements and this will not hold when we introduce other factor i.e. sequencing run, BMI, parity, gestational age (i.e. Days or trimester) and conception age , those five factors should be placed here
blocks: This should just be a vector giving the group of each sample (i.e. the motherid vector; motherid is strictly accounting for personID but not for pregnancy per se).
block_data: This data frame contains per-block metadata, with one row per block (motherid). It should only contain metadata pertaining to the blocks (i.e. T1Dstatus). motherid is not numeric, ensure that the row names match the factor names in the motherid vector (blocks).
metadata_order: This is needed if you want to specify a particular order that the model should be fit in. Metadata earlier in the list will be fit and residualized first, so these should be features we are NOT interested in and want to control for.
Results from PERMANOVA test with repeat measure-aware permutations - Controlling for Days/Trimester, sequencing run, conception age, BMI, parity and HLA type
Here the blocking factor is taking into account each mother who might have given samples from different trimesters or two different pregnancies (i.e. motherid is the name of the factor). Therefore, the factor "motherid" takes into account two different pregnancies from the same mother as one SubjectID to adjust for repeated measurements
The interaction between T1D status and time was also included in order to test if the differences between T1D and non-T1D women in the same or changes throguhout pregnancy.
6.1.1 Interaction between T1D status and Time
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 1.49 0.372 1.84 0.050 0.492
Days 1 0.27 0.270 1.33 0.009 0.217
T1D_Time_Interaction 1 0.70 0.702 3.47 0.023 0.004 **
Age 1 0.53 0.535 2.64 0.018 0.493
Parity 1 0.54 0.535 2.64 0.018 0.616
BMI 1 0.53 0.527 2.60 0.018 0.998
HLA 2 1.13 0.563 2.78 0.038 0.080 .
T1Dstatus 1 0.30 0.300 1.48 0.010 0.885
Residuals 121 24.49 0.202 0.817 0.186
Total 133 29.97 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1[1] 0.004Due to the interaction between T1D and time having a significant P-value, differences in beta diversity between T1D and non-T1D was assessed by trimester using a normal PERMANOVA with the adonis function.
6.1.2 T1D status in trimester 1
Call:
adonis(formula = D ~ SeqRun + Nulliparous + Age_LMP + BMI_conception + HLA.6DRML + T1Dstatus, data = Meta_dfTri)
Permutation: free
Number of permutations: 999
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
SeqRun 3 0.55 0.184 0.792 0.110 0.88
Nulliparous 1 0.33 0.329 1.417 0.066 0.10
Age_LMP 1 0.23 0.234 1.009 0.047 0.45
BMI_conception 1 0.25 0.255 1.098 0.051 0.35
HLA.6DRML 2 0.34 0.172 0.743 0.069 0.89
T1Dstatus 1 0.27 0.274 1.181 0.055 0.28
Residuals 13 3.02 0.232 0.603
Total 22 5.01 1.000 [1] 0.283Beta diversity Plot
6.1.3 T1D status in trimester 2
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 3 1.07 0.356 1.89 0.117 0.001 ***
Age 1 0.29 0.290 1.55 0.032 0.172
Parity 1 0.34 0.340 1.81 0.037 0.001 ***
BMI 1 0.21 0.213 1.13 0.023 0.680
HLA 2 0.68 0.339 1.80 0.074 0.074 .
T1Dstatus 1 0.36 0.361 1.92 0.039 0.105
Residuals 33 6.20 0.188 0.678 0.031 *
Total 42 9.15 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
6.1.4 T1D status in trimester 3
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 0.86 0.214 0.962 0.056 0.566
Age 1 0.24 0.240 1.078 0.016 0.386
Parity 1 0.27 0.270 1.214 0.018 0.617
BMI 1 0.39 0.385 1.734 0.025 0.874
HLA 2 0.49 0.245 1.101 0.032 0.388
T1Dstatus 1 0.45 0.451 2.030 0.029 0.003 **
Residuals 57 12.67 0.222 0.825 0.107
Total 67 15.36 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
6.1.5 Trimester 3 sensitivity analysis
For Species P-T1Dstatus= 0.008
For Strain P-T1Dstatus= 0.003
For Genus P-T1Dstatus= 0.042
For Family P-T1Dstatus= 0.041
For Order P-T1Dstatus= 0.1
For Phylum P-T1Dstatus= 0.0946.1.6 Days within T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.95 0.477 2.62 0.065 0.285
seqRun 3 1.31 0.436 2.40 0.089 0.702
Age 1 0.43 0.430 2.36 0.029 0.950
Parity 1 0.55 0.552 3.03 0.038 0.067 .
BMI 1 0.66 0.662 3.64 0.045 0.515
Days 1 0.22 0.219 1.20 0.015 0.097 .
Residuals 58 10.55 0.182 0.719 0.252
Total 67 14.68 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
6.1.7 Trimester within T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.95 0.477 2.61 0.065 0.312
seqRun 3 1.31 0.436 2.39 0.089 0.699
Age 1 0.43 0.430 2.36 0.029 0.944
Parity 1 0.55 0.552 3.03 0.038 0.043 *
BMI 1 0.66 0.662 3.63 0.045 0.526
Tri 2 0.37 0.187 1.02 0.025 0.041 *
Residuals 57 10.40 0.182 0.708 0.181
Total 67 14.68 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
6.1.8 Days within non-T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.25 0.625 3.27 0.086 0.054 .
seqRun 4 1.31 0.329 1.72 0.090 0.987
Age 1 0.65 0.652 3.41 0.045 0.015 *
Parity 1 0.47 0.470 2.46 0.032 0.737
BMI 1 0.18 0.183 0.96 0.013 1.000
Days 1 0.22 0.220 1.15 0.015 0.287
Residuals 55 10.51 0.191 0.720 0.147
Total 65 14.60 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
6.1.9 Trimester within non-T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.25 0.625 3.24 0.086 0.054 .
seqRun 4 1.31 0.329 1.70 0.090 0.975
Age 1 0.65 0.652 3.38 0.045 0.012 *
Parity 1 0.47 0.470 2.43 0.032 0.720
BMI 1 0.18 0.183 0.95 0.013 0.999
Tri 2 0.30 0.150 0.78 0.021 0.713
Residuals 54 10.43 0.193 0.714 0.272
Total 65 14.60 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
6.1.10 Other factors
6.1.10.1 Age at conception
6.1.10.1.1 Age at conception interaction with time (reference: trimester 1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.17 0.585 2.87 0.039 0.087 .
T1Dstatus 1 0.77 0.769 3.78 0.026 0.014 *
seqRun 4 1.50 0.374 1.84 0.050 0.500
Tri 2 0.39 0.193 0.95 0.013 0.628
Age 1 0.55 0.549 2.70 0.018 0.301
Parity 1 0.47 0.467 2.29 0.016 0.901
BMI 1 0.54 0.540 2.65 0.018 0.846
Age_Time_Interaction 1 0.16 0.161 0.79 0.005 0.278
Residuals 120 24.43 0.204 0.815 0.025 *
Total 133 29.97 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.1.2 Age at conception interaction with time (reference: trimester 2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.17 0.585 2.87 0.039 0.095 .
T1Dstatus 1 0.77 0.769 3.77 0.026 0.017 *
seqRun 4 1.50 0.374 1.83 0.050 0.515
Tri 2 0.39 0.193 0.95 0.013 0.596
Age 1 0.55 0.549 2.69 0.018 0.289
Parity 1 0.47 0.467 2.29 0.016 0.905
BMI 1 0.54 0.540 2.64 0.018 0.851
Age_Time_Interaction 1 0.10 0.098 0.48 0.003 0.470
Residuals 120 24.49 0.204 0.817 0.032 *
Total 133 29.97 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.1.3 Age at conception interaction with time (reference: trimester 3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.17 0.585 2.87 0.039 0.086 .
T1Dstatus 1 0.77 0.769 3.77 0.026 0.022 *
seqRun 4 1.50 0.374 1.84 0.050 0.512
Tri 2 0.39 0.193 0.95 0.013 0.602
Age 1 0.55 0.549 2.69 0.018 0.286
Parity 1 0.47 0.467 2.29 0.016 0.919
BMI 1 0.54 0.540 2.65 0.018 0.842
Age_Time_Interaction 1 0.12 0.125 0.61 0.004 0.544
Residuals 120 24.47 0.204 0.816 0.038 *
Total 133 29.97 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.1.4 Age at conception (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.17 0.585 2.88 0.039 0.091 .
T1Dstatus 1 0.77 0.769 3.78 0.026 0.020 *
seqRun 4 1.50 0.374 1.84 0.050 0.524
Tri 2 0.39 0.193 0.95 0.013 0.621
Parity 1 0.47 0.468 2.30 0.016 0.933
BMI 1 0.53 0.533 2.62 0.018 0.833
Age 1 0.56 0.555 2.73 0.019 0.288
Residuals 121 24.59 0.203 0.821 0.023 *
Total 133 29.97 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.1.5 Age at conception (no interaction: trimester 1)
Call:
adonis(formula = D ~ SeqRun + Nulliparous + BMI_conception + HLA.6DRML + T1Dstatus + Age_LMP, data = Meta_dfTri)
Permutation: free
Number of permutations: 999
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
SeqRun 3 0.55 0.184 0.792 0.110 0.88
Nulliparous 1 0.33 0.329 1.417 0.066 0.10
BMI_conception 1 0.26 0.263 1.133 0.053 0.29
HLA.6DRML 2 0.38 0.190 0.817 0.076 0.79
T1Dstatus 1 0.29 0.288 1.241 0.058 0.20
Age_LMP 1 0.18 0.178 0.765 0.035 0.77
Residuals 13 3.02 0.232 0.603
Total 22 5.01 1.000 6.1.10.1.6 Age at conception (no interaction: trimester 2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.73 0.366 1.95 0.080 0.083 .
T1Dstatus 1 0.43 0.435 2.31 0.048 0.046 *
seqRun 3 0.98 0.325 1.73 0.107 0.700
Parity 1 0.29 0.293 1.56 0.032 0.891
BMI 1 0.22 0.217 1.16 0.024 0.501
Age 1 0.30 0.296 1.58 0.032 0.278
Residuals 33 6.20 0.188 0.678 0.038 *
Total 42 9.15 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.2 Age at conception (no interaction: trimester 3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.56 0.282 1.270 0.037 0.189
T1Dstatus 1 0.44 0.435 1.958 0.028 0.006 **
seqRun 4 0.85 0.213 0.957 0.055 0.819
Parity 1 0.27 0.271 1.220 0.018 0.513
BMI 1 0.33 0.331 1.490 0.022 0.959
Age 1 0.24 0.238 1.069 0.015 0.317
Residuals 57 12.67 0.222 0.825 0.107
Total 67 15.36 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.3 Body max index (BMI)
6.1.10.3.1 BMI interaction with time (reference: trimester 1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.17 0.585 2.87 0.039 0.114
T1Dstatus 1 0.77 0.769 3.77 0.026 0.021 *
seqRun 4 1.50 0.374 1.84 0.050 0.520
Tri 2 0.39 0.193 0.95 0.013 0.659
Age 1 0.55 0.549 2.69 0.018 0.289
Parity 1 0.47 0.467 2.29 0.016 0.905
BMI 1 0.54 0.540 2.65 0.018 0.834
BMI_Time_Interaction 1 0.12 0.119 0.59 0.004 0.597
Residuals 120 24.47 0.204 0.817 0.046 *
Total 133 29.97 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.3.2 BMI interaction with time (reference: trimester 2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.17 0.585 2.87 0.039 0.096 .
T1Dstatus 1 0.77 0.769 3.77 0.026 0.018 *
seqRun 4 1.50 0.374 1.83 0.050 0.500
Tri 2 0.39 0.193 0.95 0.013 0.612
Age 1 0.55 0.549 2.69 0.018 0.293
Parity 1 0.47 0.467 2.29 0.016 0.914
BMI 1 0.54 0.540 2.65 0.018 0.832
BMI_Time_Interaction 1 0.10 0.102 0.50 0.003 0.895
Residuals 120 24.49 0.204 0.817 0.042 *
Total 133 29.97 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.3.3 BMI interaction with time (reference: trimester 3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.17 0.585 2.88 0.039 0.093 .
T1Dstatus 1 0.77 0.769 3.78 0.026 0.017 *
seqRun 4 1.50 0.374 1.84 0.050 0.527
Tri 2 0.39 0.193 0.95 0.013 0.636
Age 1 0.55 0.549 2.70 0.018 0.280
Parity 1 0.47 0.467 2.30 0.016 0.922
BMI 1 0.54 0.540 2.66 0.018 0.845
BMI_Time_Interaction 1 0.20 0.197 0.97 0.007 0.290
Residuals 120 24.39 0.203 0.814 0.025 *
Total 133 29.97 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.3.4 BMI (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.17 0.585 2.88 0.039 0.093 .
T1Dstatus 1 0.77 0.769 3.78 0.026 0.025 *
seqRun 4 1.50 0.374 1.84 0.050 0.517
Tri 2 0.39 0.193 0.95 0.013 0.634
Age 1 0.55 0.549 2.70 0.018 0.309
Parity 1 0.47 0.467 2.30 0.016 0.901
BMI 1 0.54 0.540 2.66 0.018 0.850
Residuals 121 24.59 0.203 0.821 0.043 *
Total 133 29.97 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.4 HLA type
6.1.10.4.1 HLA type interaction with time (reference: DR34 )
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.17 0.585 2.89 0.039 0.084 .
T1Dstatus 1 0.77 0.769 3.79 0.026 0.018 *
Days 1 0.28 0.280 1.38 0.009 0.282
seqRun 4 1.47 0.367 1.81 0.049 0.495
Age 1 0.54 0.543 2.68 0.018 0.352
Parity 1 0.48 0.478 2.36 0.016 0.875
BMI 1 0.53 0.531 2.62 0.018 0.860
HLA_Time_Interaction 1 0.19 0.193 0.95 0.006 1.000
Residuals 121 24.54 0.203 0.819 0.231
Total 133 29.97 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.4.2 HLA type interaction with time (reference: DRXX)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.17 0.585 2.88 0.039 0.105
T1Dstatus 1 0.77 0.769 3.78 0.026 0.017 *
Days 1 0.28 0.280 1.38 0.009 0.344
seqRun 4 1.47 0.367 1.80 0.049 0.510
Age 1 0.54 0.543 2.67 0.018 0.350
Parity 1 0.48 0.478 2.35 0.016 0.872
BMI 1 0.53 0.531 2.61 0.018 0.832
HLA_Time_Interaction 1 0.12 0.122 0.60 0.004 1.000
Residuals 121 24.61 0.203 0.821 0.314
Total 133 29.97 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.4.3 HLA type interaction with time (reference: Group3o4)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.17 0.585 2.88 0.039 0.094 .
T1Dstatus 1 0.77 0.769 3.78 0.026 0.022 *
Days 1 0.28 0.280 1.38 0.009 0.299
seqRun 4 1.47 0.367 1.80 0.049 0.490
Age 1 0.54 0.543 2.67 0.018 0.339
Parity 1 0.48 0.478 2.35 0.016 0.884
BMI 1 0.53 0.531 2.61 0.018 0.840
HLA_Time_Interaction 1 0.15 0.154 0.76 0.005 0.998
Residuals 121 24.58 0.203 0.820 0.066 .
Total 133 29.97 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.4.4 HLA type (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
Days 1 0.32 0.318 1.57 0.011 0.130
seqRun 4 1.44 0.360 1.77 0.048 0.743
Age 1 0.54 0.538 2.66 0.018 0.469
Parity 1 0.54 0.537 2.65 0.018 0.375
BMI 1 0.58 0.579 2.86 0.019 0.955
T1Dstatus 1 0.67 0.673 3.32 0.022 0.045 *
HLA 2 1.15 0.576 2.84 0.038 0.067 .
Residuals 122 24.73 0.203 0.825 0.020 *
Total 133 29.97 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.4.5 HLA (no interaction: T1)
Call:
adonis(formula = D ~ SeqRun + Nulliparous + BMI_conception + T1Dstatus + Age_LMP + HLA.6DRML, data = Meta_df)
Permutation: free
Number of permutations: 999
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
SeqRun 3 0.55 0.184 0.792 0.110 0.886
Nulliparous 1 0.33 0.329 1.417 0.066 0.097 .
BMI_conception 1 0.26 0.263 1.133 0.053 0.296
T1Dstatus 1 0.32 0.322 1.389 0.064 0.099 .
Age_LMP 1 0.19 0.188 0.810 0.038 0.717
HLA.6DRML 2 0.33 0.167 0.721 0.067 0.923
Residuals 13 3.02 0.232 0.603
Total 22 5.01 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.4.6 HLA type (no interaction: T2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
Days 1 0.30 0.296 1.56 0.032 0.56
seqRun 3 1.05 0.351 1.85 0.115 0.46
Age 1 0.29 0.289 1.53 0.032 0.51
Parity 1 0.33 0.333 1.76 0.036 0.81
BMI 1 0.22 0.220 1.16 0.024 0.88
T1Dstatus 1 0.32 0.324 1.71 0.035 0.17
HLA 2 0.58 0.289 1.52 0.063 0.23
Residuals 32 6.06 0.189 0.662 0.17
Total 42 9.15 1.000 6.1.10.4.7 HLA type (no interaction: T3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
Days 1 0.30 0.302 1.349 0.020 0.70
seqRun 4 0.83 0.208 0.931 0.054 0.58
Age 1 0.24 0.236 1.054 0.015 0.44
Parity 1 0.27 0.274 1.223 0.018 0.52
BMI 1 0.38 0.375 1.678 0.024 0.95
T1Dstatus 1 0.30 0.300 1.341 0.020 0.16
HLA 2 0.51 0.256 1.143 0.033 0.29
Residuals 56 12.53 0.224 0.816 0.40
Total 67 15.36 1.000 6.1.10.5 Parity
6.1.10.5.1 Parity interaction with time
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.17 0.585 2.89 0.039 0.102
T1Dstatus 1 0.77 0.769 3.79 0.026 0.012 *
Days 1 0.28 0.280 1.38 0.009 0.311
seqRun 4 1.47 0.367 1.81 0.049 0.485
Age 1 0.54 0.543 2.68 0.018 0.343
Parity 1 0.48 0.478 2.36 0.016 0.866
BMI 1 0.53 0.531 2.62 0.018 0.836
Parity_Time_Interaction 1 0.19 0.193 0.95 0.006 0.151
Residuals 121 24.54 0.203 0.819 0.020 *
Total 133 29.97 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.5.2 Parity (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.17 0.585 2.89 0.039 0.083 .
T1Dstatus 1 0.77 0.769 3.79 0.026 0.014 *
Days 1 0.28 0.280 1.38 0.009 0.318
seqRun 4 1.47 0.367 1.81 0.049 0.492
BMI 1 0.60 0.597 2.95 0.020 0.896
Age 1 0.55 0.547 2.70 0.018 0.394
Parity 1 0.41 0.407 2.01 0.014 0.801
Residuals 122 24.73 0.203 0.825 0.016 *
Total 133 29.97 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.6 Mode of delivery
6.1.10.6.1 Mode of delivery interaction with time (reference: Emergency caesarea)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.17 0.585 2.95 0.039 0.101
T1Dstatus 1 0.77 0.769 3.87 0.026 0.020 *
MOD 2 0.99 0.496 2.50 0.033 0.317
Days 1 0.29 0.288 1.45 0.010 0.226
seqRun 4 1.36 0.339 1.71 0.045 0.857
Age 1 0.66 0.663 3.34 0.022 0.006 **
Parity 1 0.41 0.411 2.07 0.014 0.971
BMI 1 0.51 0.514 2.59 0.017 0.810
MOD_Time_Interaction 1 0.19 0.193 0.97 0.006 1.000
Residuals 119 23.61 0.198 0.788 0.206
Total 133 29.97 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.6.2 Mode of delivery interaction with time (reference: Elective caesarea)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.17 0.585 2.94 0.039 0.096 .
T1Dstatus 1 0.77 0.769 3.86 0.026 0.022 *
MOD 2 0.99 0.496 2.50 0.033 0.304
Days 1 0.29 0.288 1.45 0.010 0.236
seqRun 4 1.36 0.339 1.71 0.045 0.849
Age 1 0.66 0.663 3.33 0.022 0.006 **
Parity 1 0.41 0.411 2.07 0.014 0.976
BMI 1 0.51 0.514 2.58 0.017 0.818
MOD_Time_Interaction 1 0.13 0.129 0.65 0.004 1.000
Residuals 119 23.67 0.199 0.790 0.293
Total 133 29.97 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.6.3 Mode of delivery interaction with time (reference: Labour)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.17 0.585 2.94 0.039 0.098 .
T1Dstatus 1 0.77 0.769 3.86 0.026 0.020 *
MOD 2 0.99 0.496 2.50 0.033 0.299
Days 1 0.29 0.288 1.45 0.010 0.191
seqRun 4 1.36 0.339 1.71 0.045 0.850
Age 1 0.66 0.663 3.33 0.022 0.005 **
Parity 1 0.41 0.411 2.07 0.014 0.979
BMI 1 0.51 0.514 2.58 0.017 0.829
MOD_Time_Interaction 1 0.13 0.132 0.67 0.004 1.000
Residuals 119 23.67 0.199 0.790 0.306
Total 133 29.97 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.6.4 Mode of delivery (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
Days 1 0.32 0.318 1.60 0.011 0.119
seqRun 4 1.44 0.360 1.81 0.048 0.736
Age 1 0.54 0.538 2.71 0.018 0.462
Parity 1 0.54 0.537 2.71 0.018 0.365
BMI 1 0.58 0.579 2.92 0.019 0.954
HLA 2 1.07 0.537 2.71 0.036 0.135
T1Dstatus 1 0.75 0.751 3.78 0.025 0.009 **
MOD 2 0.93 0.464 2.34 0.031 0.365
Residuals 120 23.80 0.198 0.794 0.033 *
Total 133 29.97 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.6.5 Mode of delivery (no interaction: T1)
Call:
adonis(formula = D ~ SeqRun + Nulliparous + BMI_conception + T1Dstatus + Age_LMP + HLA.6DRML + MOD, data = Meta_df)
Permutation: free
Number of permutations: 999
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
SeqRun 3 0.55 0.184 0.822 0.110 0.848
Nulliparous 1 0.33 0.329 1.471 0.066 0.085 .
BMI_conception 1 0.26 0.263 1.177 0.053 0.262
T1Dstatus 1 0.32 0.322 1.442 0.064 0.087 .
Age_LMP 1 0.19 0.188 0.841 0.038 0.689
HLA.6DRML 2 0.33 0.167 0.748 0.067 0.889
MOD 2 0.56 0.279 1.248 0.111 0.147
Residuals 11 2.46 0.224 0.491
Total 22 5.01 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.6.6 Mode of delivery (no interaction: T2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
Days 1 0.30 0.296 1.60 0.032 0.537
seqRun 3 1.05 0.351 1.89 0.115 0.463
Age 1 0.29 0.289 1.56 0.032 0.461
Parity 1 0.33 0.333 1.79 0.036 0.816
BMI 1 0.22 0.220 1.19 0.024 0.892
HLA 2 0.54 0.268 1.45 0.059 0.360
T1Dstatus 1 0.36 0.364 1.97 0.040 0.062 .
MOD 2 0.49 0.247 1.33 0.054 0.510
Residuals 30 5.56 0.185 0.608 0.222
Total 42 9.15 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.6.7 Mode of delivery (no interaction: T3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
Days 1 0.30 0.302 1.374 0.020 0.705
seqRun 4 0.83 0.208 0.948 0.054 0.568
Age 1 0.24 0.236 1.073 0.015 0.450
Parity 1 0.27 0.274 1.245 0.018 0.505
BMI 1 0.38 0.375 1.709 0.024 0.951
HLA 2 0.48 0.239 1.089 0.031 0.425
T1Dstatus 1 0.33 0.333 1.515 0.022 0.071 .
MOD 2 0.66 0.332 1.512 0.043 0.022 *
Residuals 54 11.86 0.220 0.772 0.068 .
Total 67 15.36 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.7 Carbohydrate intake
6.1.10.7.1 Carbohydrate interaction with time (reference: trimester 1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.18 0.591 2.93 0.040 0.104
T1Dstatus 1 0.79 0.790 3.91 0.027 0.016 *
Carbs 1 0.46 0.455 2.26 0.015 0.487
seqRun 4 1.54 0.385 1.91 0.052 0.525
Tri 2 0.39 0.193 0.95 0.013 0.568
Age 1 0.53 0.532 2.64 0.018 0.470
Parity 1 0.45 0.452 2.24 0.015 0.926
BMI 1 0.54 0.544 2.70 0.018 0.624
Carb_Time_Interaction 1 0.10 0.098 0.49 0.003 0.997
Residuals 117 23.61 0.202 0.798 0.072 .
Total 131 29.58 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.7.2 Carbohydrate interaction with time (reference: trimester 2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.18 0.591 2.93 0.040 0.090 .
T1Dstatus 1 0.79 0.790 3.91 0.027 0.016 *
Carbs 1 0.46 0.455 2.25 0.015 0.463
seqRun 4 1.54 0.385 1.90 0.052 0.507
Tri 2 0.39 0.193 0.95 0.013 0.515
Age 1 0.53 0.532 2.64 0.018 0.462
Parity 1 0.45 0.452 2.24 0.015 0.937
BMI 1 0.54 0.544 2.69 0.018 0.645
Carb_Time_Interaction 1 0.08 0.077 0.38 0.003 1.000
Residuals 117 23.63 0.202 0.799 0.131
Total 131 29.58 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.7.3 Carbohydrate interaction with time (reference: trimester 3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.18 0.591 2.93 0.040 0.104
T1Dstatus 1 0.79 0.790 3.91 0.027 0.015 *
Carbs 1 0.46 0.455 2.26 0.015 0.500
seqRun 4 1.54 0.385 1.91 0.052 0.510
Tri 2 0.39 0.193 0.95 0.013 0.543
Age 1 0.53 0.532 2.64 0.018 0.491
Parity 1 0.45 0.452 2.24 0.015 0.931
BMI 1 0.54 0.544 2.70 0.018 0.620
Carb_Time_Interaction 1 0.09 0.092 0.46 0.003 1.000
Residuals 117 23.61 0.202 0.798 0.103
Total 131 29.58 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.7.4 Carbohydrate (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 1.53 0.383 1.91 0.052 0.501
Tri 2 0.43 0.216 1.08 0.015 0.420
Age 1 0.55 0.552 2.75 0.019 0.430
Parity 1 0.54 0.541 2.69 0.018 0.550
BMI 1 0.56 0.556 2.77 0.019 0.990
HLA 2 1.07 0.536 2.67 0.036 0.162
T1Dstatus 1 0.78 0.776 3.86 0.026 0.013 *
Carbs 1 0.42 0.415 2.07 0.014 0.513
Residuals 118 23.71 0.201 0.801 0.027 *
Total 131 29.58 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.8 Fibre intake
6.1.10.8.1 Fibre interaction with time (reference: trimester 1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.18 0.591 2.93 0.040 0.093 .
T1Dstatus 1 0.79 0.790 3.91 0.027 0.013 *
Fiber 1 0.43 0.426 2.11 0.014 0.598
seqRun 4 1.52 0.381 1.89 0.051 0.577
Tri 2 0.39 0.195 0.97 0.013 0.514
Age 1 0.57 0.568 2.81 0.019 0.197
Parity 1 0.47 0.470 2.33 0.016 0.893
BMI 1 0.52 0.521 2.58 0.018 0.774
Fiber_Time_Interaction 1 0.11 0.112 0.56 0.004 0.834
Residuals 117 23.60 0.202 0.798 0.060 .
Total 131 29.58 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.8.2 Fibre interaction with time (reference: trimester 2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.18 0.591 2.92 0.040 0.090 .
T1Dstatus 1 0.79 0.790 3.91 0.027 0.017 *
Fiber 1 0.43 0.426 2.11 0.014 0.594
seqRun 4 1.52 0.381 1.88 0.051 0.558
Tri 2 0.39 0.195 0.97 0.013 0.512
Age 1 0.57 0.568 2.81 0.019 0.211
Parity 1 0.47 0.470 2.32 0.016 0.894
BMI 1 0.52 0.521 2.58 0.018 0.754
Fiber_Time_Interaction 1 0.06 0.063 0.31 0.002 1.000
Residuals 117 23.65 0.202 0.799 0.107
Total 131 29.58 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.8.3 Fibre interaction with time (reference: trimester 3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.18 0.591 2.93 0.040 0.094 .
T1Dstatus 1 0.79 0.790 3.92 0.027 0.022 *
Fiber 1 0.43 0.426 2.11 0.014 0.587
seqRun 4 1.52 0.381 1.89 0.051 0.556
Tri 2 0.39 0.195 0.97 0.013 0.507
Age 1 0.57 0.568 2.81 0.019 0.213
Parity 1 0.47 0.470 2.33 0.016 0.878
BMI 1 0.52 0.521 2.58 0.018 0.744
Fiber_Time_Interaction 1 0.12 0.116 0.57 0.004 1.000
Residuals 117 23.60 0.202 0.798 0.133
Total 131 29.58 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.8.4 Fibre (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 1.53 0.383 1.91 0.052 0.500
Tri 2 0.43 0.216 1.07 0.015 0.446
Age 1 0.55 0.552 2.75 0.019 0.434
Parity 1 0.54 0.541 2.69 0.018 0.539
BMI 1 0.56 0.556 2.77 0.019 0.984
HLA 2 1.07 0.536 2.67 0.036 0.163
T1Dstatus 1 0.78 0.776 3.86 0.026 0.015 *
Fiber 1 0.41 0.407 2.02 0.014 0.573
Residuals 118 23.71 0.201 0.802 0.062 .
Total 131 29.58 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.9 1,5-AG (glucose control measurement)
6.1.10.9.1 1,5-AG interaction with time
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.36 0.680 3.49 0.053 0.020 *
T1Dstatus 1 0.73 0.730 3.75 0.029 0.039 *
Days 1 0.25 0.246 1.26 0.010 0.422
seqRun 3 1.32 0.441 2.26 0.052 0.808
Age 1 0.56 0.556 2.85 0.022 0.129
Parity 1 0.46 0.463 2.38 0.018 0.857
BMI 1 0.36 0.361 1.85 0.014 0.902
AG15 1 0.58 0.582 2.99 0.023 0.013 *
AG15_T1D_Interaction 1 0.37 0.367 1.88 0.014 0.554
Residuals 100 19.47 0.195 0.765 0.004 **
Total 112 25.45 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 16.1.10.9.2 1,5-AG within T1D women
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.01 0.504 2.88 0.091 0.24
Days 1 0.18 0.180 1.03 0.016 0.60
seqRun 3 1.30 0.435 2.48 0.117 0.81
Age 1 0.39 0.389 2.22 0.035 0.79
Parity 1 0.59 0.592 3.38 0.053 0.49
BMI 1 0.46 0.463 2.64 0.042 0.17
AG15 1 0.35 0.350 2.00 0.031 0.85
Residuals 39 6.83 0.175 0.615 0.38
Total 49 11.12 1.000 6.1.10.9.3 1,5-AG interaction with time (within non-T1D women)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.25 0.625 3.56 0.092 0.075 .
Days 1 0.28 0.278 1.58 0.020 0.084 .
seqRun 3 1.16 0.385 2.19 0.085 0.954
Age 1 0.67 0.674 3.84 0.049 0.015 *
Parity 1 0.46 0.458 2.61 0.034 0.761
BMI 1 0.16 0.161 0.92 0.012 1.000
AG15 1 0.56 0.555 3.16 0.041 0.868
Residuals 52 9.13 0.176 0.668 0.293
Total 62 13.66 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17 Strain taxonomic level
7.1 Microbial community composition analysis at strain level (Beta diversity analysis)
7.1.1 Interaction between T1D status and Time
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 1.41 0.352 1.66 0.045 0.485
Days 1 0.33 0.326 1.54 0.010 0.062 .
T1D_Time_Interaction 1 0.81 0.809 3.81 0.026 0.003 **
Age 1 0.55 0.547 2.58 0.017 0.510
Parity 1 0.58 0.583 2.75 0.019 0.436
BMI 1 0.49 0.491 2.32 0.016 0.998
HLA 2 1.33 0.663 3.12 0.042 0.020 *
T1Dstatus 1 0.35 0.345 1.63 0.011 0.831
Residuals 121 25.66 0.212 0.815 0.051 .
Total 133 31.50 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1[1] 0.0037.1.2 T1D status in trimester 1
Call:
adonis(formula = D ~ SeqRun + Nulliparous + Age_LMP + BMI_conception + HLA.6DRML + T1Dstatus, data = Meta_dfTri)
Permutation: free
Number of permutations: 999
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
SeqRun 3 0.54 0.179 0.718 0.100 0.96
Nulliparous 1 0.33 0.326 1.308 0.061 0.14
Age_LMP 1 0.26 0.255 1.024 0.048 0.44
BMI_conception 1 0.28 0.282 1.129 0.053 0.29
HLA.6DRML 2 0.38 0.191 0.764 0.071 0.87
T1Dstatus 1 0.33 0.329 1.320 0.062 0.14
Residuals 13 3.24 0.249 0.606
Total 22 5.35 1.000 [1] 0.135Beta diversity Plot
7.1.3 T1D status in trimester 2
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 3 1.04 0.347 1.77 0.109 0.001 ***
Age 1 0.30 0.299 1.53 0.031 0.480
Parity 1 0.36 0.360 1.83 0.038 0.001 ***
BMI 1 0.20 0.204 1.04 0.021 0.510
HLA 2 0.77 0.384 1.96 0.080 0.043 *
T1Dstatus 1 0.42 0.424 2.16 0.044 0.042 *
Residuals 33 6.47 0.196 0.676 0.007 **
Total 42 9.57 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
7.1.4 T1D status in trimester 3
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 0.87 0.217 0.929 0.054 0.481
Age 1 0.23 0.227 0.972 0.014 0.397
Parity 1 0.27 0.271 1.164 0.017 0.603
BMI 1 0.37 0.374 1.604 0.023 0.747
HLA 2 0.54 0.271 1.162 0.034 0.295
T1Dstatus 1 0.50 0.503 2.158 0.031 0.003 **
Residuals 57 13.29 0.233 0.827 0.063 .
Total 67 16.07 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
7.1.5 Days within T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.04 0.521 2.77 0.069 0.193
seqRun 3 1.21 0.405 2.15 0.080 0.882
Age 1 0.43 0.427 2.27 0.028 0.951
Parity 1 0.63 0.626 3.32 0.041 0.071 .
BMI 1 0.67 0.669 3.55 0.044 0.573
Days 1 0.24 0.239 1.27 0.016 0.055 .
Residuals 58 10.93 0.188 0.722 0.177
Total 67 15.15 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
7.1.6 Trimester within T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.04 0.521 2.76 0.069 0.189
seqRun 3 1.21 0.405 2.14 0.080 0.871
Age 1 0.43 0.427 2.26 0.028 0.947
Parity 1 0.63 0.626 3.31 0.041 0.059 .
BMI 1 0.67 0.669 3.54 0.044 0.577
Tri 2 0.39 0.196 1.04 0.026 0.045 *
Residuals 57 10.78 0.189 0.711 0.138
Total 67 15.15 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
7.1.7 Days within non-T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.38 0.689 3.39 0.089 0.047 *
seqRun 4 1.38 0.344 1.69 0.089 0.993
Age 1 0.62 0.619 3.05 0.040 0.019 *
Parity 1 0.50 0.502 2.47 0.032 0.719
BMI 1 0.21 0.212 1.04 0.014 0.998
Days 1 0.25 0.252 1.24 0.016 0.159
Residuals 55 11.18 0.203 0.720 0.135
Total 65 15.52 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
7.1.8 Trimester within non-T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.38 0.689 3.36 0.089 0.036 *
seqRun 4 1.38 0.344 1.68 0.089 0.988
Age 1 0.62 0.619 3.02 0.040 0.020 *
Parity 1 0.50 0.502 2.45 0.032 0.730
BMI 1 0.21 0.212 1.03 0.014 0.997
Tri 2 0.35 0.177 0.86 0.023 0.500
Residuals 54 11.07 0.205 0.714 0.162
Total 65 15.52 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
7.1.9 Other factors
7.1.9.1 Age at conception
7.1.9.1.1 Age at conception interaction with time (reference: trimester 1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.39 0.696 3.26 0.044 0.020 *
T1Dstatus 1 0.90 0.904 4.23 0.029 0.009 **
seqRun 4 1.41 0.353 1.65 0.045 0.608
Tri 2 0.43 0.217 1.01 0.014 0.473
Age 1 0.57 0.566 2.65 0.018 0.322
Parity 1 0.50 0.496 2.32 0.016 0.929
BMI 1 0.51 0.506 2.37 0.016 0.916
Age_Time_Interaction 1 0.16 0.157 0.73 0.005 0.381
Residuals 120 25.63 0.214 0.814 0.009 **
Total 133 31.50 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.1.2 Age at conception interaction with time (reference: trimester 2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.39 0.696 3.25 0.044 0.022 *
T1Dstatus 1 0.90 0.904 4.22 0.029 0.004 **
seqRun 4 1.41 0.353 1.65 0.045 0.630
Tri 2 0.43 0.217 1.01 0.014 0.487
Age 1 0.57 0.566 2.64 0.018 0.332
Parity 1 0.50 0.496 2.32 0.016 0.930
BMI 1 0.51 0.506 2.36 0.016 0.918
Age_Time_Interaction 1 0.10 0.099 0.46 0.003 0.539
Residuals 120 25.69 0.214 0.816 0.007 **
Total 133 31.50 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.1.3 Age at conception interaction with time (reference: trimester 3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.39 0.696 3.26 0.044 0.020 *
T1Dstatus 1 0.90 0.904 4.23 0.029 0.007 **
seqRun 4 1.41 0.353 1.65 0.045 0.596
Tri 2 0.43 0.217 1.01 0.014 0.467
Age 1 0.57 0.566 2.65 0.018 0.312
Parity 1 0.50 0.496 2.32 0.016 0.921
BMI 1 0.51 0.506 2.36 0.016 0.914
Age_Time_Interaction 1 0.12 0.123 0.57 0.004 0.587
Residuals 120 25.67 0.214 0.815 0.005 **
Total 133 31.50 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.1.4 Age at conception (no interaction and within trimester 1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.55 0.275 1.103 0.103 0.23
T1Dstatus 1 0.26 0.263 1.054 0.049 0.35
seqRun 3 0.49 0.163 0.652 0.091 0.95
Parity 1 0.31 0.308 1.235 0.058 0.57
BMI 1 0.32 0.322 1.289 0.060 0.19
Age 1 0.18 0.180 0.722 0.034 0.92
Residuals 13 3.24 0.249 0.606 0.58
Total 22 5.35 1.000 7.1.9.1.5 Age at conception (no interaction and within trimester 2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.82 0.410 2.09 0.086 0.038 *
T1Dstatus 1 0.52 0.520 2.65 0.054 0.018 *
seqRun 3 0.92 0.307 1.57 0.096 0.777
Parity 1 0.31 0.312 1.59 0.033 0.875
BMI 1 0.21 0.214 1.09 0.022 0.485
Age 1 0.31 0.310 1.58 0.032 0.287
Residuals 33 6.47 0.196 0.676 0.009 **
Total 42 9.57 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.1.6 Age at conception (no interaction and within trimester 3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.65 0.324 1.390 0.040 0.066 .
T1Dstatus 1 0.48 0.481 2.064 0.030 0.004 **
seqRun 4 0.86 0.215 0.921 0.053 0.813
Parity 1 0.26 0.260 1.116 0.016 0.732
BMI 1 0.31 0.309 1.325 0.019 0.988
Age 1 0.23 0.226 0.970 0.014 0.375
Residuals 57 13.29 0.233 0.827 0.057 .
Total 67 16.07 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.2 Body max index (BMI)
7.1.9.2.1 BMI interaction with time (reference: trimester 1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.39 0.696 3.26 0.044 0.022 *
T1Dstatus 1 0.90 0.904 4.23 0.029 0.005 **
seqRun 4 1.41 0.353 1.65 0.045 0.597
Tri 2 0.43 0.217 1.01 0.014 0.459
Age 1 0.57 0.566 2.65 0.018 0.296
Parity 1 0.50 0.496 2.32 0.016 0.925
BMI 1 0.51 0.506 2.36 0.016 0.914
BMI_Time_Interaction 1 0.13 0.134 0.63 0.004 0.394
Residuals 120 25.66 0.214 0.814 0.003 **
Total 133 31.50 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.2.2 BMI interaction with time (reference: trimester 2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.39 0.696 3.25 0.044 0.031 *
T1Dstatus 1 0.90 0.904 4.23 0.029 0.007 **
seqRun 4 1.41 0.353 1.65 0.045 0.614
Tri 2 0.43 0.217 1.01 0.014 0.450
Age 1 0.57 0.566 2.65 0.018 0.286
Parity 1 0.50 0.496 2.32 0.016 0.915
BMI 1 0.51 0.506 2.36 0.016 0.925
BMI_Time_Interaction 1 0.12 0.117 0.55 0.004 0.889
Residuals 120 25.67 0.214 0.815 0.007 **
Total 133 31.50 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.2.3 BMI interaction with time (reference: trimester 3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.39 0.696 3.27 0.044 0.021 *
T1Dstatus 1 0.90 0.904 4.24 0.029 0.003 **
seqRun 4 1.41 0.353 1.66 0.045 0.629
Tri 2 0.43 0.217 1.02 0.014 0.473
Age 1 0.57 0.566 2.66 0.018 0.295
Parity 1 0.50 0.496 2.33 0.016 0.927
BMI 1 0.51 0.506 2.37 0.016 0.927
BMI_Time_Interaction 1 0.22 0.217 1.02 0.007 0.105
Residuals 120 25.57 0.213 0.812 0.002 **
Total 133 31.50 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.2.4 BMI (no interaction but within T1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.55 0.275 1.152 0.103 0.25
T1Dstatus 1 0.26 0.263 1.101 0.049 0.35
seqRun 1 0.22 0.224 0.938 0.042 0.61
Age 1 0.23 0.233 0.974 0.043 0.87
Parity 1 0.27 0.266 1.114 0.050 0.74
BMI 1 0.23 0.234 0.979 0.044 0.69
Residuals 15 3.58 0.239 0.669 0.54
Total 22 5.35 1.000 7.1.9.2.5 BMI (no interaction but within T2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.82 0.410 2.04 0.086 0.042 *
T1Dstatus 1 0.52 0.520 2.59 0.054 0.012 *
seqRun 1 0.40 0.402 2.01 0.042 0.907
Age 1 0.31 0.309 1.54 0.032 0.302
Parity 1 0.31 0.307 1.53 0.032 0.875
BMI 1 0.20 0.205 1.02 0.021 0.395
Residuals 35 7.01 0.200 0.732 0.010 **
Total 42 9.57 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.2.6 BMI (no interaction but within T3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.65 0.324 1.392 0.040 0.066 .
T1Dstatus 1 0.48 0.481 2.067 0.030 0.002 **
seqRun 1 0.17 0.166 0.713 0.010 0.033 *
Age 1 0.25 0.250 1.074 0.016 0.565
Parity 1 0.26 0.256 1.099 0.016 0.632
BMI 1 0.30 0.305 1.309 0.019 0.977
Residuals 60 13.97 0.233 0.869 0.006 **
Total 67 16.07 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.3 HLA type
7.1.9.3.1 HLA type interaction with time (reference: DR34 )
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.39 0.696 3.27 0.044 0.025 *
T1Dstatus 1 0.90 0.904 4.25 0.029 0.006 **
Days 1 0.33 0.335 1.57 0.011 0.173
seqRun 4 1.37 0.344 1.62 0.044 0.544
Age 1 0.56 0.559 2.63 0.018 0.336
Parity 1 0.51 0.509 2.39 0.016 0.862
BMI 1 0.49 0.494 2.32 0.016 0.918
HLA_Time_Interaction 1 0.20 0.196 0.92 0.006 1.000
Residuals 121 25.74 0.213 0.817 0.068 .
Total 133 31.50 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.3.2 HLA type interaction with time (reference: DRXX)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.39 0.696 3.26 0.044 0.036 *
T1Dstatus 1 0.90 0.904 4.24 0.029 0.007 **
Days 1 0.33 0.335 1.57 0.011 0.160
seqRun 4 1.37 0.344 1.61 0.044 0.545
Age 1 0.56 0.559 2.62 0.018 0.348
Parity 1 0.51 0.509 2.38 0.016 0.878
BMI 1 0.49 0.494 2.31 0.016 0.916
HLA_Time_Interaction 1 0.12 0.121 0.57 0.004 1.000
Residuals 121 25.81 0.213 0.819 0.101
Total 133 31.50 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.3.3 HLA type interaction with time (reference: Group3o4)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.39 0.696 3.27 0.044 0.032 *
T1Dstatus 1 0.90 0.904 4.25 0.029 0.007 **
Days 1 0.33 0.335 1.57 0.011 0.173
seqRun 4 1.37 0.344 1.61 0.044 0.547
Age 1 0.56 0.559 2.62 0.018 0.347
Parity 1 0.51 0.509 2.39 0.016 0.902
BMI 1 0.49 0.494 2.32 0.016 0.922
HLA_Time_Interaction 1 0.16 0.159 0.75 0.005 1.000
Residuals 121 25.77 0.213 0.818 0.030 *
Total 133 31.50 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.3.4 HLA type (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
Days 1 0.38 0.383 1.80 0.012 0.034 *
seqRun 4 1.35 0.338 1.59 0.043 0.664
Age 1 0.55 0.550 2.59 0.017 0.492
Parity 1 0.58 0.578 2.72 0.018 0.272
BMI 1 0.55 0.553 2.60 0.018 0.971
T1Dstatus 1 0.80 0.797 3.75 0.025 0.019 *
HLA 2 1.35 0.677 3.19 0.043 0.026 *
Residuals 122 25.93 0.213 0.823 0.002 **
Total 133 31.50 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.4 Parity
7.1.9.4.1 Parity interaction with time
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.39 0.696 3.27 0.044 0.023 *
T1Dstatus 1 0.90 0.904 4.25 0.029 0.007 **
Days 1 0.33 0.335 1.57 0.011 0.134
seqRun 4 1.37 0.344 1.61 0.044 0.524
Age 1 0.56 0.559 2.63 0.018 0.366
Parity 1 0.51 0.509 2.39 0.016 0.885
BMI 1 0.49 0.494 2.32 0.016 0.912
Parity_Time_Interaction 1 0.19 0.190 0.89 0.006 0.087 .
Residuals 121 25.74 0.213 0.817 0.001 ***
Total 133 31.50 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.4.2 Parity (no interaction but within T1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.55 0.275 1.152 0.103 0.24
T1Dstatus 1 0.26 0.263 1.101 0.049 0.34
seqRun 1 0.22 0.224 0.938 0.042 0.58
Age 1 0.23 0.233 0.974 0.043 0.85
BMI 1 0.25 0.246 1.031 0.046 0.87
Parity 1 0.25 0.254 1.063 0.047 0.48
Residuals 15 3.58 0.239 0.669 0.53
Total 22 5.35 1.000 7.1.9.4.3 Parity (no interaction but within T2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.82 0.410 2.04 0.086 0.050 *
T1Dstatus 1 0.52 0.520 2.59 0.054 0.014 *
seqRun 1 0.40 0.402 2.01 0.042 0.875
Age 1 0.31 0.309 1.54 0.032 0.299
BMI 1 0.28 0.281 1.40 0.029 0.298
Parity 1 0.23 0.231 1.15 0.024 0.958
Residuals 35 7.01 0.200 0.732 0.010 **
Total 42 9.57 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.4.4 Parity (no interaction but within T3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.65 0.324 1.392 0.040 0.073 .
T1Dstatus 1 0.48 0.481 2.067 0.030 0.009 **
seqRun 1 0.17 0.166 0.713 0.010 0.029 *
Age 1 0.25 0.250 1.074 0.016 0.573
BMI 1 0.30 0.305 1.309 0.019 0.980
Parity 1 0.26 0.256 1.099 0.016 0.731
Residuals 60 13.97 0.233 0.869 0.005 **
Total 67 16.07 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.5 Mode of delivery
7.1.9.5.1 Mode of delivery interaction with time (reference: Emergency caesarea)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.39 0.696 3.36 0.044 0.022 *
T1Dstatus 1 0.90 0.904 4.36 0.029 0.004 **
MOD 2 1.00 0.501 2.42 0.032 0.401
Days 1 0.34 0.344 1.66 0.011 0.116
seqRun 4 1.33 0.332 1.60 0.042 0.708
Age 1 0.74 0.741 3.57 0.024 0.001 ***
Parity 1 0.42 0.419 2.02 0.013 0.987
BMI 1 0.48 0.479 2.31 0.015 0.902
MOD_Time_Interaction 1 0.20 0.204 0.98 0.006 1.000
Residuals 119 24.69 0.207 0.784 0.022 *
Total 133 31.50 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.5.2 Mode of delivery interaction with time (reference: Elective caesarea)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.39 0.696 3.35 0.044 0.025 *
T1Dstatus 1 0.90 0.904 4.34 0.029 0.006 **
MOD 2 1.00 0.501 2.41 0.032 0.400
Days 1 0.34 0.344 1.65 0.011 0.104
seqRun 4 1.33 0.332 1.59 0.042 0.727
Age 1 0.74 0.741 3.56 0.024 0.003 **
Parity 1 0.42 0.419 2.01 0.013 0.989
BMI 1 0.48 0.479 2.30 0.015 0.909
MOD_Time_Interaction 1 0.12 0.123 0.59 0.004 1.000
Residuals 119 24.77 0.208 0.786 0.078 .
Total 133 31.50 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.5.3 Mode of delivery interaction with time (reference: Labour)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.39 0.696 3.35 0.044 0.022 *
T1Dstatus 1 0.90 0.904 4.34 0.029 0.002 **
MOD 2 1.00 0.501 2.41 0.032 0.416
Days 1 0.34 0.344 1.65 0.011 0.105
seqRun 4 1.33 0.332 1.59 0.042 0.735
Age 1 0.74 0.741 3.56 0.024 0.001 ***
Parity 1 0.42 0.419 2.01 0.013 0.986
BMI 1 0.48 0.479 2.30 0.015 0.885
MOD_Time_Interaction 1 0.12 0.123 0.59 0.004 1.000
Residuals 119 24.77 0.208 0.786 0.111
Total 133 31.50 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.5.4 Mode of delivery (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
Days 1 0.38 0.383 1.84 0.012 0.042 *
seqRun 4 1.35 0.338 1.63 0.043 0.664
Age 1 0.55 0.550 2.65 0.017 0.490
Parity 1 0.58 0.578 2.79 0.018 0.276
BMI 1 0.55 0.553 2.67 0.018 0.965
HLA 2 1.28 0.638 3.08 0.040 0.048 *
T1Dstatus 1 0.88 0.876 4.22 0.028 0.007 **
MOD 2 1.04 0.521 2.51 0.033 0.277
Residuals 120 24.89 0.207 0.790 0.002 **
Total 133 31.50 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.6 Carbohydrate intake
7.1.9.6.1 Carbohydrate interaction with time (reference: trimester 1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.40 0.699 3.29 0.045 0.039 *
T1Dstatus 1 0.93 0.929 4.37 0.030 0.001 ***
Carbs 1 0.42 0.423 1.99 0.014 0.684
seqRun 4 1.45 0.362 1.70 0.047 0.611
Tri 2 0.43 0.216 1.02 0.014 0.390
Age 1 0.52 0.524 2.46 0.017 0.670
Parity 1 0.47 0.471 2.22 0.015 0.946
BMI 1 0.52 0.516 2.43 0.017 0.737
Carb_Time_Interaction 1 0.10 0.100 0.47 0.003 0.994
Residuals 117 24.87 0.213 0.799 0.036 *
Total 131 31.11 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.6.2 Carbohydrate interaction with time (reference: trimester 2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.40 0.699 3.29 0.045 0.017 *
T1Dstatus 1 0.93 0.929 4.37 0.030 0.007 **
Carbs 1 0.42 0.423 1.99 0.014 0.650
seqRun 4 1.45 0.362 1.70 0.047 0.620
Tri 2 0.43 0.216 1.02 0.014 0.404
Age 1 0.52 0.524 2.46 0.017 0.634
Parity 1 0.47 0.471 2.22 0.015 0.954
BMI 1 0.52 0.516 2.43 0.017 0.752
Carb_Time_Interaction 1 0.10 0.097 0.46 0.003 1.000
Residuals 117 24.87 0.213 0.799 0.047 *
Total 131 31.11 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.6.3 Carbohydrate interaction with time (reference: trimester 3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.40 0.699 3.29 0.045 0.022 *
T1Dstatus 1 0.93 0.929 4.37 0.030 0.004 **
Carbs 1 0.42 0.423 1.99 0.014 0.677
seqRun 4 1.45 0.362 1.70 0.047 0.596
Tri 2 0.43 0.216 1.02 0.014 0.396
Age 1 0.52 0.524 2.46 0.017 0.670
Parity 1 0.47 0.471 2.22 0.015 0.953
BMI 1 0.52 0.516 2.43 0.017 0.760
Carb_Time_Interaction 1 0.10 0.105 0.49 0.003 0.996
Residuals 117 24.86 0.213 0.799 0.036 *
Total 131 31.11 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.6.4 Carbohydrate (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 1.45 0.363 1.71 0.047 0.495
Tri 2 0.48 0.240 1.13 0.015 0.260
Age 1 0.57 0.566 2.67 0.018 0.446
Parity 1 0.58 0.580 2.74 0.019 0.464
BMI 1 0.54 0.544 2.57 0.017 0.949
HLA 2 1.28 0.639 3.02 0.041 0.046 *
T1Dstatus 1 0.91 0.908 4.29 0.029 0.005 **
Carbs 1 0.34 0.336 1.59 0.011 0.856
Residuals 118 24.97 0.212 0.803 0.015 *
Total 131 31.11 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.7 Fibre intake
7.1.9.7.1 Fibre interaction with time (reference: trimester 1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.40 0.699 3.30 0.045 0.022 *
T1Dstatus 1 0.93 0.929 4.38 0.030 0.007 **
Fiber 1 0.42 0.421 1.98 0.014 0.682
seqRun 4 1.42 0.354 1.67 0.046 0.734
Tri 2 0.44 0.219 1.03 0.014 0.357
Age 1 0.55 0.553 2.60 0.018 0.446
Parity 1 0.50 0.496 2.34 0.016 0.914
BMI 1 0.51 0.509 2.40 0.016 0.782
Fiber_Time_Interaction 1 0.12 0.115 0.54 0.004 0.795
Residuals 117 24.83 0.212 0.798 0.009 **
Total 131 31.11 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.7.2 Fibre interaction with time (reference: trimester 2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.40 0.699 3.29 0.045 0.014 *
T1Dstatus 1 0.93 0.929 4.37 0.030 0.009 **
Fiber 1 0.42 0.421 1.98 0.014 0.675
seqRun 4 1.42 0.354 1.67 0.046 0.744
Tri 2 0.44 0.219 1.03 0.014 0.316
Age 1 0.55 0.553 2.60 0.018 0.436
Parity 1 0.50 0.496 2.33 0.016 0.895
BMI 1 0.51 0.509 2.39 0.016 0.795
Fiber_Time_Interaction 1 0.07 0.069 0.32 0.002 1.000
Residuals 117 24.88 0.213 0.800 0.026 *
Total 131 31.11 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.7.3 Fibre interaction with time (reference: trimester 3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.40 0.699 3.29 0.045 0.025 *
T1Dstatus 1 0.93 0.929 4.37 0.030 0.004 **
Fiber 1 0.42 0.421 1.98 0.014 0.680
seqRun 4 1.42 0.354 1.67 0.046 0.731
Tri 2 0.44 0.219 1.03 0.014 0.357
Age 1 0.55 0.553 2.60 0.018 0.446
Parity 1 0.50 0.496 2.34 0.016 0.892
BMI 1 0.51 0.509 2.40 0.016 0.776
Fiber_Time_Interaction 1 0.10 0.105 0.49 0.003 1.000
Residuals 117 24.84 0.212 0.799 0.033 *
Total 131 31.11 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.7.4 Fibre (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 1.45 0.363 1.72 0.047 0.609
Tri 2 0.48 0.240 1.14 0.015 0.282
Age 1 0.57 0.566 2.68 0.018 0.465
Parity 1 0.58 0.580 2.74 0.019 0.462
BMI 1 0.54 0.544 2.57 0.017 0.954
HLA 2 1.28 0.639 3.02 0.041 0.045 *
T1Dstatus 1 0.91 0.908 4.29 0.029 0.002 **
Fiber 1 0.36 0.356 1.68 0.011 0.835
Residuals 118 24.95 0.211 0.802 0.013 *
Total 131 31.11 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.8 1,5-AG (glucose control measurement)
7.1.9.8.1 1,5-AG interaction with time
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.60 0.799 3.90 0.060 0.004 **
T1Dstatus 1 0.84 0.841 4.10 0.031 0.015 *
Days 1 0.29 0.287 1.40 0.011 0.230
seqRun 3 1.24 0.413 2.02 0.046 0.920
Age 1 0.57 0.573 2.80 0.021 0.114
Parity 1 0.46 0.464 2.26 0.017 0.875
BMI 1 0.36 0.361 1.76 0.013 0.928
AG15 1 0.55 0.554 2.70 0.021 0.021 *
AG15_T1D_Interaction 1 0.33 0.335 1.63 0.013 0.960
Residuals 100 20.49 0.205 0.766 0.002 **
Total 112 26.74 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.8.2 1,5-AG within T1D women
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.16 0.581 3.21 0.101 0.092 .
Days 1 0.21 0.210 1.16 0.018 0.364
seqRun 3 1.23 0.411 2.27 0.107 0.890
Age 1 0.39 0.385 2.13 0.033 0.880
Parity 1 0.61 0.614 3.40 0.053 0.390
BMI 1 0.48 0.483 2.67 0.042 0.188
AG15 1 0.38 0.384 2.12 0.033 0.895
Residuals 39 7.05 0.181 0.612 0.227
Total 49 11.52 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 17.1.9.8.3 1,5-AG interaction with time (within non-T1D women)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 1.36 0.682 3.63 0.095 0.058 .
Days 1 0.29 0.294 1.57 0.020 0.107
seqRun 3 1.17 0.390 2.08 0.081 0.984
Age 1 0.68 0.677 3.61 0.047 0.020 *
Parity 1 0.47 0.471 2.51 0.033 0.830
BMI 1 0.18 0.182 0.97 0.013 1.000
AG15 1 0.50 0.504 2.69 0.035 0.878
Residuals 52 9.76 0.188 0.677 0.271
Total 62 14.42 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18 Genus taxonomic level
8.1 Microbial community composition analysis at Genus level (Beta diversity analysis)
8.1.1 Interaction between T1D status and Time
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 0.66 0.166 1.68 0.045 0.507
Days 1 0.20 0.203 2.05 0.014 0.158
T1D_Time_Interaction 1 0.44 0.439 4.45 0.030 0.006 **
Age 1 0.38 0.383 3.88 0.026 0.619
Parity 1 0.22 0.223 2.26 0.015 0.028 *
BMI 1 0.35 0.354 3.58 0.024 1.000
HLA 2 0.40 0.201 2.03 0.027 0.387
T1Dstatus 1 0.12 0.120 1.22 0.008 0.786
Residuals 121 11.95 0.099 0.811 0.444
Total 133 14.74 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1[1] 0.0068.1.2 T1D status in trimester 1
Call:
adonis(formula = D ~ SeqRun + Nulliparous + Age_LMP + BMI_conception + HLA.6DRML + T1Dstatus, data = Meta_dfTri)
Permutation: free
Number of permutations: 999
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
SeqRun 3 0.255 0.0848 0.750 0.101 0.80
Nulliparous 1 0.148 0.1483 1.311 0.059 0.22
Age_LMP 1 0.164 0.1637 1.448 0.065 0.17
BMI_conception 1 0.120 0.1202 1.063 0.048 0.38
HLA.6DRML 2 0.195 0.0976 0.863 0.077 0.65
T1Dstatus 1 0.169 0.1694 1.498 0.067 0.17
Residuals 13 1.470 0.1131 0.583
Total 22 2.521 1.000 [1] 0.167Beta diversity Plot
8.1.3 T1D status in trimester 2
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 3 0.67 0.2226 2.39 0.143 0.001 ***
Age 1 0.18 0.1810 1.94 0.039 0.675
Parity 1 0.13 0.1256 1.35 0.027 0.001 ***
BMI 1 0.10 0.1002 1.08 0.021 0.648
HLA 2 0.31 0.1570 1.69 0.067 0.198
T1Dstatus 1 0.22 0.2164 2.32 0.046 0.085 .
Residuals 33 3.07 0.0932 0.657 0.081 .
Total 42 4.68 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
8.1.4 T1D status in trimester 3
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 0.31 0.078 0.73 0.043 0.50
Age 1 0.14 0.141 1.33 0.019 0.13
Parity 1 0.18 0.175 1.66 0.024 0.14
BMI 1 0.34 0.341 3.22 0.047 0.88
HLA 2 0.11 0.053 0.50 0.015 0.96
T1Dstatus 1 0.17 0.173 1.64 0.024 0.12
Residuals 57 6.04 0.106 0.829 0.83
Total 67 7.29 1.000 Beta diversity Plot
8.1.5 Days within T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.27 0.134 1.72 0.041 0.738
seqRun 3 0.67 0.224 2.88 0.102 0.432
Age 1 0.26 0.262 3.37 0.040 0.674
Parity 1 0.17 0.170 2.19 0.026 0.119
BMI 1 0.55 0.551 7.10 0.084 0.481
Days 1 0.16 0.157 2.02 0.024 0.018 *
Residuals 58 4.50 0.078 0.684 0.395
Total 67 6.58 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
8.1.6 Trimester within T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.27 0.134 1.71 0.041 0.785
seqRun 3 0.67 0.224 2.86 0.102 0.400
Age 1 0.26 0.262 3.35 0.040 0.656
Parity 1 0.17 0.170 2.18 0.026 0.124
BMI 1 0.55 0.551 7.05 0.084 0.493
Tri 2 0.20 0.101 1.29 0.031 0.024 *
Residuals 57 4.46 0.078 0.677 0.348
Total 67 6.58 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
8.1.7 Days within non-T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.66 0.329 3.14 0.085 0.129
seqRun 4 0.47 0.117 1.12 0.061 0.994
Age 1 0.50 0.505 4.82 0.065 0.017 *
Parity 1 0.11 0.112 1.07 0.015 0.959
BMI 1 0.09 0.094 0.90 0.012 0.998
Days 1 0.12 0.115 1.10 0.015 0.351
Residuals 55 5.76 0.105 0.747 0.309
Total 65 7.72 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
8.1.8 Trimester within non-T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.66 0.329 3.12 0.085 0.120
seqRun 4 0.47 0.117 1.11 0.061 0.994
Age 1 0.50 0.505 4.79 0.065 0.012 *
Parity 1 0.11 0.112 1.06 0.015 0.951
BMI 1 0.09 0.094 0.89 0.012 0.998
Tri 2 0.18 0.090 0.86 0.023 0.630
Residuals 54 5.70 0.106 0.738 0.417
Total 65 7.72 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
8.1.9 Other factors
8.1.9.1 Age at conception
8.1.9.1.1 Age at conception interaction with time (reference: trimester 1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.47 0.236 2.37 0.032 0.341
T1Dstatus 1 0.45 0.448 4.50 0.030 0.025 *
seqRun 4 0.66 0.164 1.65 0.045 0.653
Tri 2 0.21 0.103 1.03 0.014 0.564
Age 1 0.41 0.410 4.12 0.028 0.312
Parity 1 0.17 0.172 1.73 0.012 0.918
BMI 1 0.37 0.366 3.67 0.025 0.934
Age_Time_Interaction 1 0.06 0.063 0.63 0.004 0.630
Residuals 120 11.95 0.100 0.810 0.294
Total 133 14.74 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.1.2 Age at conception interaction with time (reference: trimester 2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.47 0.236 2.37 0.032 0.342
T1Dstatus 1 0.45 0.448 4.49 0.030 0.033 *
seqRun 4 0.66 0.164 1.65 0.045 0.649
Tri 2 0.21 0.103 1.03 0.014 0.566
Age 1 0.41 0.410 4.12 0.028 0.322
Parity 1 0.17 0.172 1.72 0.012 0.905
BMI 1 0.37 0.366 3.67 0.025 0.915
Age_Time_Interaction 1 0.04 0.043 0.43 0.003 0.693
Residuals 120 11.97 0.100 0.812 0.303
Total 133 14.74 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.1.3 Age at conception interaction with time (reference: trimester 3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.47 0.236 2.38 0.032 0.362
T1Dstatus 1 0.45 0.448 4.50 0.030 0.038 *
seqRun 4 0.66 0.164 1.65 0.045 0.663
Tri 2 0.21 0.103 1.03 0.014 0.585
Age 1 0.41 0.410 4.13 0.028 0.328
Parity 1 0.17 0.172 1.73 0.012 0.929
BMI 1 0.37 0.366 3.68 0.025 0.904
Age_Time_Interaction 1 0.07 0.072 0.73 0.005 0.368
Residuals 120 11.94 0.099 0.810 0.291
Total 133 14.74 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.1.4 Age at conception (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.47 0.236 2.38 0.032 0.346
T1Dstatus 1 0.45 0.448 4.51 0.030 0.045 *
seqRun 4 0.66 0.164 1.66 0.045 0.643
Tri 2 0.21 0.103 1.04 0.014 0.549
Parity 1 0.17 0.173 1.74 0.012 0.937
BMI 1 0.36 0.364 3.66 0.025 0.900
Age 1 0.41 0.412 4.15 0.028 0.331
Residuals 121 12.01 0.099 0.815 0.278
Total 133 14.74 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.2 Body max index (BMI)
8.1.9.2.1 BMI interaction with time (reference: trimester 1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.47 0.236 2.37 0.032 0.375
T1Dstatus 1 0.45 0.448 4.49 0.030 0.029 *
seqRun 4 0.66 0.164 1.65 0.045 0.640
Tri 2 0.21 0.103 1.03 0.014 0.553
Age 1 0.41 0.410 4.12 0.028 0.299
Parity 1 0.17 0.172 1.72 0.012 0.933
BMI 1 0.37 0.366 3.67 0.025 0.921
BMI_Time_Interaction 1 0.04 0.041 0.41 0.003 0.829
Residuals 120 11.97 0.100 0.812 0.315
Total 133 14.74 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.2.2 BMI interaction with time (reference: trimester 2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.47 0.236 2.37 0.032 0.351
T1Dstatus 1 0.45 0.448 4.49 0.030 0.025 *
seqRun 4 0.66 0.164 1.65 0.045 0.636
Tri 2 0.21 0.103 1.03 0.014 0.548
Age 1 0.41 0.410 4.12 0.028 0.308
Parity 1 0.17 0.172 1.72 0.012 0.909
BMI 1 0.37 0.366 3.67 0.025 0.939
BMI_Time_Interaction 1 0.05 0.050 0.50 0.003 0.629
Residuals 120 11.96 0.100 0.811 0.277
Total 133 14.74 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.2.3 BMI interaction with time (reference: trimester 3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.47 0.236 2.38 0.032 0.326
T1Dstatus 1 0.45 0.448 4.51 0.030 0.028 *
seqRun 4 0.66 0.164 1.66 0.045 0.660
Tri 2 0.21 0.103 1.04 0.014 0.557
Age 1 0.41 0.410 4.14 0.028 0.341
Parity 1 0.17 0.172 1.73 0.012 0.922
BMI 1 0.37 0.366 3.69 0.025 0.935
BMI_Time_Interaction 1 0.11 0.106 1.06 0.007 0.242
Residuals 120 11.90 0.099 0.808 0.231
Total 133 14.74 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.2.4 BMI (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.47 0.236 2.38 0.032 0.346
T1Dstatus 1 0.45 0.448 4.51 0.030 0.029 *
seqRun 4 0.66 0.164 1.66 0.045 0.655
Tri 2 0.21 0.103 1.04 0.014 0.559
Age 1 0.41 0.410 4.14 0.028 0.303
Parity 1 0.17 0.172 1.73 0.012 0.913
BMI 1 0.37 0.366 3.69 0.025 0.925
Residuals 121 12.01 0.099 0.815 0.272
Total 133 14.74 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.3 HLA type
8.1.9.3.1 HLA type interaction with time (reference: DR34 )
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.47 0.236 2.39 0.032 0.360
T1Dstatus 1 0.45 0.448 4.52 0.030 0.036 *
Days 1 0.24 0.242 2.44 0.016 0.130
seqRun 4 0.61 0.152 1.53 0.041 0.667
Age 1 0.40 0.398 4.01 0.027 0.323
Parity 1 0.18 0.176 1.78 0.012 0.903
BMI 1 0.35 0.351 3.54 0.024 0.939
HLA_Time_Interaction 1 0.06 0.062 0.63 0.004 1.000
Residuals 121 11.99 0.099 0.813 0.430
Total 133 14.74 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.3.2 HLA type interaction with time (reference: DRXX)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.47 0.236 2.39 0.032 0.346
T1Dstatus 1 0.45 0.448 4.52 0.030 0.033 *
Days 1 0.24 0.242 2.45 0.016 0.129
seqRun 4 0.61 0.152 1.53 0.041 0.708
Age 1 0.40 0.398 4.02 0.027 0.345
Parity 1 0.18 0.176 1.78 0.012 0.894
BMI 1 0.35 0.351 3.54 0.024 0.932
HLA_Time_Interaction 1 0.07 0.071 0.72 0.005 1.000
Residuals 121 11.98 0.099 0.813 0.417
Total 133 14.74 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.3.3 HLA type interaction with time (reference: Group3o4)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.47 0.236 2.39 0.032 0.344
T1Dstatus 1 0.45 0.448 4.52 0.030 0.028 *
Days 1 0.24 0.242 2.44 0.016 0.126
seqRun 4 0.61 0.152 1.53 0.041 0.687
Age 1 0.40 0.398 4.01 0.027 0.319
Parity 1 0.18 0.176 1.78 0.012 0.894
BMI 1 0.35 0.351 3.54 0.024 0.927
HLA_Time_Interaction 1 0.06 0.062 0.63 0.004 0.775
Residuals 121 11.99 0.099 0.813 0.165
Total 133 14.74 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.3.4 HLA type (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
Days 1 0.27 0.266 2.69 0.018 0.076 .
seqRun 4 0.60 0.150 1.52 0.041 0.701
Age 1 0.39 0.389 3.94 0.026 0.616
Parity 1 0.24 0.235 2.38 0.016 0.009 **
BMI 1 0.43 0.431 4.36 0.029 0.995
T1Dstatus 1 0.37 0.374 3.79 0.025 0.068 .
HLA 2 0.40 0.199 2.01 0.027 0.468
Residuals 122 12.05 0.099 0.817 0.196
Total 133 14.74 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.4 Parity
8.1.9.4.1 Parity interaction with time
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.47 0.236 2.40 0.032 0.357
T1Dstatus 1 0.45 0.448 4.54 0.030 0.031 *
Days 1 0.24 0.242 2.46 0.016 0.117
seqRun 4 0.61 0.152 1.54 0.041 0.683
Age 1 0.40 0.398 4.03 0.027 0.336
Parity 1 0.18 0.176 1.78 0.012 0.912
BMI 1 0.35 0.351 3.55 0.024 0.931
Parity_Time_Interaction 1 0.12 0.119 1.21 0.008 0.064 .
Residuals 121 11.93 0.099 0.809 0.132
Total 133 14.74 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.4.2 Parity (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.47 0.236 2.39 0.032 0.353
T1Dstatus 1 0.45 0.448 4.53 0.030 0.032 *
Days 1 0.24 0.242 2.45 0.016 0.139
seqRun 4 0.61 0.152 1.53 0.041 0.690
BMI 1 0.36 0.363 3.67 0.025 0.901
Age 1 0.40 0.398 4.03 0.027 0.354
Parity 1 0.16 0.163 1.65 0.011 0.930
Residuals 122 12.05 0.099 0.817 0.191
Total 133 14.74 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.4.3 Parity (no interaction but within T1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.266 0.133 1.239 0.106 0.26
T1Dstatus 1 0.079 0.079 0.735 0.031 0.74
seqRun 1 0.164 0.164 1.526 0.065 0.25
Age 1 0.137 0.137 1.276 0.054 0.81
BMI 1 0.158 0.158 1.467 0.063 0.32
Parity 1 0.106 0.106 0.988 0.042 0.45
Residuals 15 1.611 0.107 0.639 0.48
Total 22 2.521 1.000 8.1.9.4.4 Parity (no interaction but within T2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.33 0.1648 1.690 0.070 0.316
T1Dstatus 1 0.29 0.2885 2.957 0.062 0.044 *
seqRun 1 0.20 0.2032 2.084 0.043 0.911
Age 1 0.21 0.2144 2.197 0.046 0.128
BMI 1 0.16 0.1571 1.611 0.034 0.206
Parity 1 0.07 0.0725 0.743 0.015 0.668
Residuals 35 3.41 0.0975 0.730 0.103
Total 42 4.68 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.4.5 Parity (no interaction but within T3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.15 0.0748 0.709 0.021 0.857
T1Dstatus 1 0.20 0.2020 1.915 0.028 0.065 .
seqRun 1 0.04 0.0374 0.355 0.005 0.104
Age 1 0.15 0.1533 1.453 0.021 0.635
BMI 1 0.23 0.2270 2.152 0.031 0.954
Parity 1 0.19 0.1859 1.762 0.026 0.867
Residuals 60 6.33 0.1055 0.869 0.722
Total 67 7.29 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.5 Mode of delivery
8.1.9.5.1 Mode of delivery interaction with time (reference: Emergency caesarea)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.47 0.236 2.44 0.032 0.366
T1Dstatus 1 0.45 0.448 4.62 0.030 0.023 *
MOD 2 0.33 0.163 1.68 0.022 0.765
Days 1 0.24 0.245 2.53 0.017 0.121
seqRun 4 0.62 0.156 1.61 0.042 0.628
Age 1 0.54 0.541 5.58 0.037 0.002 **
Parity 1 0.19 0.190 1.96 0.013 0.690
BMI 1 0.30 0.304 3.14 0.021 0.955
MOD_Time_Interaction 1 0.07 0.067 0.70 0.005 0.997
Residuals 119 11.53 0.097 0.782 0.287
Total 133 14.74 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.5.2 Mode of delivery interaction with time (reference: Elective caesarea)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.47 0.236 2.44 0.032 0.354
T1Dstatus 1 0.45 0.448 4.63 0.030 0.024 *
MOD 2 0.33 0.163 1.68 0.022 0.766
Days 1 0.24 0.245 2.53 0.017 0.106
seqRun 4 0.62 0.156 1.61 0.042 0.624
Age 1 0.54 0.541 5.59 0.037 0.003 **
Parity 1 0.19 0.190 1.96 0.013 0.719
BMI 1 0.30 0.304 3.14 0.021 0.950
MOD_Time_Interaction 1 0.08 0.083 0.86 0.006 1.000
Residuals 119 11.51 0.097 0.781 0.424
Total 133 14.74 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.5.3 Mode of delivery interaction with time (reference: Labour)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.47 0.236 2.44 0.032 0.309
T1Dstatus 1 0.45 0.448 4.62 0.030 0.028 *
MOD 2 0.33 0.163 1.68 0.022 0.764
Days 1 0.24 0.245 2.52 0.017 0.122
seqRun 4 0.62 0.156 1.61 0.042 0.611
Age 1 0.54 0.541 5.58 0.037 0.004 **
Parity 1 0.19 0.190 1.96 0.013 0.697
BMI 1 0.30 0.304 3.13 0.021 0.963
MOD_Time_Interaction 1 0.06 0.055 0.57 0.004 1.000
Residuals 119 11.54 0.097 0.783 0.475
Total 133 14.74 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.5.4 Mode of delivery (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
Days 1 0.27 0.266 2.75 0.018 0.080 .
seqRun 4 0.60 0.150 1.56 0.041 0.697
Age 1 0.39 0.389 4.03 0.026 0.630
Parity 1 0.24 0.235 2.43 0.016 0.007 **
BMI 1 0.43 0.431 4.46 0.029 0.988
HLA 2 0.40 0.201 2.08 0.027 0.446
T1Dstatus 1 0.37 0.369 3.82 0.025 0.056 .
MOD 2 0.45 0.227 2.35 0.031 0.276
Residuals 120 11.59 0.097 0.786 0.150
Total 133 14.74 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.6 Carbohydrate intake
8.1.9.6.1 Carbohydrate interaction with time (reference: trimester 1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.47 0.235 2.37 0.032 0.36
T1Dstatus 1 0.43 0.434 4.36 0.030 0.04 *
Carbs 1 0.19 0.190 1.91 0.013 0.53
seqRun 4 0.64 0.160 1.61 0.044 0.75
Tri 2 0.21 0.106 1.06 0.014 0.45
Age 1 0.42 0.416 4.19 0.028 0.29
Parity 1 0.17 0.174 1.74 0.012 0.86
BMI 1 0.37 0.374 3.76 0.026 0.74
Carb_Time_Interaction 1 0.08 0.080 0.80 0.005 0.70
Residuals 117 11.64 0.099 0.796 0.32
Total 131 14.63 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.6.2 Carbohydrate interaction with time (reference: trimester 2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.47 0.235 2.36 0.032 0.318
T1Dstatus 1 0.43 0.434 4.34 0.030 0.045 *
Carbs 1 0.19 0.190 1.91 0.013 0.550
seqRun 4 0.64 0.160 1.61 0.044 0.730
Tri 2 0.21 0.106 1.06 0.014 0.428
Age 1 0.42 0.416 4.17 0.028 0.323
Parity 1 0.17 0.174 1.74 0.012 0.858
BMI 1 0.37 0.374 3.75 0.026 0.729
Carb_Time_Interaction 1 0.04 0.041 0.41 0.003 0.992
Residuals 117 11.68 0.100 0.798 0.377
Total 131 14.63 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.6.3 Carbohydrate interaction with time (reference: trimester 3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.47 0.235 2.36 0.032 0.356
T1Dstatus 1 0.43 0.434 4.35 0.030 0.045 *
Carbs 1 0.19 0.190 1.91 0.013 0.526
seqRun 4 0.64 0.160 1.61 0.044 0.724
Tri 2 0.21 0.106 1.06 0.014 0.461
Age 1 0.42 0.416 4.18 0.028 0.325
Parity 1 0.17 0.174 1.74 0.012 0.866
BMI 1 0.37 0.374 3.75 0.026 0.734
Carb_Time_Interaction 1 0.05 0.053 0.53 0.004 0.984
Residuals 117 11.67 0.100 0.797 0.397
Total 131 14.63 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.6.4 Carbohydrate (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 0.67 0.168 1.70 0.046 0.508
Tri 2 0.23 0.113 1.13 0.015 0.455
Age 1 0.41 0.413 4.16 0.028 0.522
Parity 1 0.23 0.227 2.29 0.016 0.015 *
BMI 1 0.41 0.406 4.08 0.028 0.981
HLA 2 0.40 0.201 2.03 0.027 0.457
T1Dstatus 1 0.36 0.359 3.61 0.025 0.054 .
Carbs 1 0.21 0.206 2.07 0.014 0.392
Residuals 118 11.72 0.099 0.801 0.265
Total 131 14.63 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.7 Fibre intake
8.1.9.7.1 Fibre interaction with time (reference: trimester 1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.47 0.235 2.36 0.032 0.362
T1Dstatus 1 0.43 0.434 4.35 0.030 0.029 *
Fiber 1 0.16 0.157 1.58 0.011 0.684
seqRun 4 0.64 0.160 1.60 0.044 0.714
Tri 2 0.21 0.105 1.05 0.014 0.472
Age 1 0.45 0.449 4.51 0.031 0.117
Parity 1 0.18 0.177 1.78 0.012 0.832
BMI 1 0.35 0.349 3.50 0.024 0.837
Fiber_Time_Interaction 1 0.08 0.084 0.84 0.006 0.209
Residuals 117 11.66 0.100 0.797 0.283
Total 131 14.63 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.7.2 Fibre interaction with time (reference: trimester 2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.47 0.235 2.35 0.032 0.345
T1Dstatus 1 0.43 0.434 4.33 0.030 0.043 *
Fiber 1 0.16 0.157 1.57 0.011 0.694
seqRun 4 0.64 0.160 1.60 0.044 0.749
Tri 2 0.21 0.105 1.05 0.014 0.468
Age 1 0.45 0.449 4.49 0.031 0.120
Parity 1 0.18 0.177 1.77 0.012 0.822
BMI 1 0.35 0.349 3.49 0.024 0.836
Fiber_Time_Interaction 1 0.03 0.026 0.26 0.002 0.993
Residuals 117 11.72 0.100 0.801 0.407
Total 131 14.63 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.7.3 Fibre interaction with time (reference: trimester 3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.47 0.235 2.37 0.032 0.361
T1Dstatus 1 0.43 0.434 4.36 0.030 0.038 *
Fiber 1 0.16 0.157 1.58 0.011 0.714
seqRun 4 0.64 0.160 1.61 0.044 0.736
Tri 2 0.21 0.105 1.06 0.014 0.490
Age 1 0.45 0.449 4.51 0.031 0.124
Parity 1 0.18 0.177 1.78 0.012 0.838
BMI 1 0.35 0.349 3.51 0.024 0.819
Fiber_Time_Interaction 1 0.10 0.102 1.02 0.007 0.901
Residuals 117 11.64 0.100 0.796 0.408
Total 131 14.63 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.7.4 Fibre (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 0.67 0.168 1.69 0.046 0.53
Tri 2 0.23 0.113 1.13 0.015 0.43
Age 1 0.41 0.413 4.15 0.028 0.51
Parity 1 0.23 0.227 2.29 0.016 0.02 *
BMI 1 0.41 0.406 4.08 0.028 0.99
HLA 2 0.40 0.201 2.02 0.027 0.46
T1Dstatus 1 0.36 0.359 3.61 0.025 0.07 .
Fiber 1 0.18 0.181 1.81 0.012 0.52
Residuals 118 11.74 0.100 0.803 0.32
Total 131 14.63 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.8 1,5-AG (glucose control measurement)
8.1.9.8.1 1,5-AG interaction with time
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.52 0.262 2.80 0.042 0.281
T1Dstatus 1 0.52 0.522 5.56 0.042 0.018 *
Days 1 0.14 0.143 1.53 0.012 0.478
seqRun 3 0.54 0.179 1.91 0.043 0.879
Age 1 0.44 0.438 4.67 0.035 0.043 *
Parity 1 0.16 0.165 1.76 0.013 0.927
BMI 1 0.23 0.230 2.46 0.019 0.934
AG15 1 0.28 0.285 3.04 0.023 0.021 *
AG15_T1D_Interaction 1 0.17 0.172 1.83 0.014 0.145
Residuals 100 9.37 0.094 0.757 0.029 *
Total 112 12.39 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.8.2 1,5-AG within T1D women
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.32 0.161 2.19 0.068 0.486
Days 1 0.11 0.113 1.54 0.024 0.225
seqRun 3 0.45 0.151 2.06 0.095 0.937
Age 1 0.25 0.249 3.39 0.052 0.055 .
Parity 1 0.20 0.201 2.74 0.042 0.229
BMI 1 0.41 0.411 5.60 0.087 0.124
AG15 1 0.14 0.136 1.86 0.029 0.800
Residuals 39 2.86 0.073 0.603 0.392
Total 49 4.75 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 18.1.9.8.3 1,5-AG interaction with time (within non-T1D women)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.59 0.296 3.06 0.083 0.193
Days 1 0.11 0.105 1.09 0.015 0.558
seqRun 3 0.48 0.159 1.65 0.067 0.887
Age 1 0.48 0.480 4.96 0.067 0.053 .
Parity 1 0.12 0.120 1.24 0.017 0.972
BMI 1 0.08 0.076 0.79 0.011 1.000
AG15 1 0.29 0.292 3.01 0.041 0.793
Residuals 52 5.04 0.097 0.701 0.672
Total 62 7.18 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19 Family taxonomic level
9.1 Microbial community composition analysis at Family level (Beta diversity analysis)
9.1.1 Interaction between T1D status and Time
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 0.57 0.142 1.85 0.050 0.615
Days 1 0.18 0.184 2.40 0.016 0.131
T1D_Time_Interaction 1 0.39 0.391 5.11 0.034 0.004 **
Age 1 0.27 0.274 3.58 0.024 0.838
Parity 1 0.16 0.165 2.15 0.014 0.030 *
BMI 1 0.22 0.218 2.84 0.019 1.000
HLA 2 0.27 0.133 1.74 0.023 0.524
T1Dstatus 1 0.06 0.065 0.85 0.006 0.895
Residuals 121 9.26 0.077 0.813 0.578
Total 133 11.39 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1[1] 0.0049.1.2 T1D status in trimester 1
Call:
adonis(formula = D ~ SeqRun + Nulliparous + Age_LMP + BMI_conception + HLA.6DRML + T1Dstatus, data = Meta_dfTri)
Permutation: free
Number of permutations: 999
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
SeqRun 3 0.240 0.0800 0.901 0.118 0.58
Nulliparous 1 0.162 0.1622 1.827 0.080 0.11
Age_LMP 1 0.123 0.1234 1.389 0.061 0.20
BMI_conception 1 0.070 0.0703 0.792 0.035 0.59
HLA.6DRML 2 0.162 0.0808 0.909 0.080 0.55
T1Dstatus 1 0.117 0.1169 1.317 0.058 0.26
Residuals 13 1.154 0.0888 0.569
Total 22 2.029 1.000 [1] 0.258Beta diversity Plot
9.1.3 T1D status in trimester 2
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 3 0.55 0.1820 2.580 0.154 0.060 .
Age 1 0.12 0.1153 1.635 0.033 0.668
Parity 1 0.11 0.1081 1.533 0.031 0.011 *
BMI 1 0.06 0.0623 0.883 0.018 0.687
HLA 2 0.21 0.1056 1.498 0.060 0.271
T1Dstatus 1 0.17 0.1658 2.351 0.047 0.096 .
Residuals 33 2.33 0.0705 0.658 0.130
Total 42 3.54 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
9.1.4 T1D status in trimester 3
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 0.24 0.0612 0.75 0.043 0.634
Age 1 0.09 0.0924 1.13 0.016 0.156
Parity 1 0.14 0.1438 1.75 0.026 0.156
BMI 1 0.28 0.2779 3.39 0.049 0.790
HLA 2 0.05 0.0246 0.30 0.009 0.996
T1Dstatus 1 0.15 0.1540 1.88 0.027 0.068 .
Residuals 57 4.68 0.0821 0.829 0.864
Total 67 5.64 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
9.1.5 Days within T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.20 0.098 1.73 0.040 0.679
seqRun 3 0.62 0.205 3.63 0.127 0.463
Age 1 0.12 0.123 2.19 0.025 0.805
Parity 1 0.13 0.129 2.29 0.027 0.131
BMI 1 0.36 0.355 6.29 0.073 0.548
Days 1 0.16 0.163 2.88 0.033 0.011 *
Residuals 58 3.27 0.056 0.674 0.242
Total 67 4.86 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
9.1.6 Trimester within T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.20 0.098 1.72 0.040 0.682
seqRun 3 0.62 0.205 3.60 0.127 0.460
Age 1 0.12 0.123 2.17 0.025 0.817
Parity 1 0.13 0.129 2.27 0.027 0.099 .
BMI 1 0.36 0.355 6.24 0.073 0.547
Tri 2 0.19 0.096 1.69 0.040 0.020 *
Residuals 57 3.24 0.057 0.668
Total 67 4.86 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
9.1.7 Days within non-T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.49 0.244 2.82 0.079 0.169
seqRun 4 0.40 0.101 1.16 0.065 0.950
Age 1 0.34 0.341 3.94 0.055 0.047 *
Parity 1 0.05 0.054 0.63 0.009 0.972
BMI 1 0.05 0.048 0.55 0.008 1.000
Days 1 0.08 0.083 0.96 0.013 0.425
Residuals 55 4.76 0.087 0.771 0.455
Total 65 6.18 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
9.1.8 Trimester within non-T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.49 0.244 2.80 0.079 0.184
seqRun 4 0.40 0.101 1.15 0.065 0.947
Age 1 0.34 0.341 3.90 0.055 0.048 *
Parity 1 0.05 0.054 0.62 0.009 0.983
BMI 1 0.05 0.048 0.55 0.008 0.999
Tri 2 0.13 0.066 0.76 0.021 0.745
Residuals 54 4.71 0.087 0.763 0.641
Total 65 6.18 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
9.1.9 Other factors
9.1.9.1 Age at conception
9.1.9.1.1 Age at conception interaction with time (reference: trimester 1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.33 0.165 2.13 0.029 0.397
T1Dstatus 1 0.34 0.340 4.40 0.030 0.051 .
seqRun 4 0.60 0.149 1.93 0.052 0.562
Tri 2 0.16 0.081 1.04 0.014 0.565
Age 1 0.30 0.296 3.83 0.026 0.436
Parity 1 0.12 0.119 1.54 0.010 0.937
BMI 1 0.23 0.226 2.92 0.020 0.960
Age_Time_Interaction 1 0.04 0.042 0.55 0.004 0.697
Residuals 120 9.28 0.077 0.815 0.475
Total 133 11.39 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.1.2 Age at conception interaction with time (reference: trimester 2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.33 0.165 2.13 0.029 0.43
T1Dstatus 1 0.34 0.340 4.39 0.030 0.05 *
seqRun 4 0.60 0.149 1.92 0.052 0.55
Tri 2 0.16 0.081 1.04 0.014 0.60
Age 1 0.30 0.296 3.83 0.026 0.46
Parity 1 0.12 0.119 1.54 0.010 0.94
BMI 1 0.23 0.226 2.91 0.020 0.96
Age_Time_Interaction 1 0.02 0.023 0.30 0.002 0.88
Residuals 120 9.30 0.078 0.816 0.48
Total 133 11.39 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.1.3 Age at conception interaction with time (reference: trimester 3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.33 0.165 2.14 0.029 0.427
T1Dstatus 1 0.34 0.340 4.40 0.030 0.048 *
seqRun 4 0.60 0.149 1.93 0.052 0.544
Tri 2 0.16 0.081 1.04 0.014 0.592
Age 1 0.30 0.296 3.84 0.026 0.436
Parity 1 0.12 0.119 1.55 0.010 0.928
BMI 1 0.23 0.226 2.92 0.020 0.967
Age_Time_Interaction 1 0.05 0.052 0.67 0.005 0.375
Residuals 120 9.27 0.077 0.814 0.393
Total 133 11.39 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.1.4 Age at conception (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.33 0.165 2.14 0.029 0.390
T1Dstatus 1 0.34 0.340 4.42 0.030 0.054 .
seqRun 4 0.60 0.149 1.93 0.052 0.547
Tri 2 0.16 0.081 1.05 0.014 0.571
Parity 1 0.12 0.121 1.57 0.011 0.925
BMI 1 0.23 0.226 2.94 0.020 0.957
Age 1 0.29 0.294 3.82 0.026 0.440
Residuals 121 9.32 0.077 0.818 0.401
Total 133 11.39 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.2 Body max index (BMI)
9.1.9.2.1 BMI interaction with time (reference: trimester 1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.33 0.165 2.13 0.029 0.426
T1Dstatus 1 0.34 0.340 4.39 0.030 0.055 .
seqRun 4 0.60 0.149 1.92 0.052 0.557
Tri 2 0.16 0.081 1.04 0.014 0.599
Age 1 0.30 0.296 3.82 0.026 0.440
Parity 1 0.12 0.119 1.54 0.010 0.943
BMI 1 0.23 0.226 2.91 0.020 0.959
BMI_Time_Interaction 1 0.02 0.017 0.21 0.001 0.968
Residuals 120 9.31 0.078 0.817 0.499
Total 133 11.39 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.2.2 BMI interaction with time (reference: trimester 2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.33 0.165 2.13 0.029 0.406
T1Dstatus 1 0.34 0.340 4.40 0.030 0.048 *
seqRun 4 0.60 0.149 1.93 0.052 0.545
Tri 2 0.16 0.081 1.04 0.014 0.592
Age 1 0.30 0.296 3.83 0.026 0.438
Parity 1 0.12 0.119 1.54 0.010 0.922
BMI 1 0.23 0.226 2.92 0.020 0.967
BMI_Time_Interaction 1 0.04 0.041 0.53 0.004 0.505
Residuals 120 9.28 0.077 0.815 0.411
Total 133 11.39 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.2.3 BMI interaction with time (reference: trimester 3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.33 0.165 2.14 0.029 0.430
T1Dstatus 1 0.34 0.340 4.42 0.030 0.042 *
seqRun 4 0.60 0.149 1.94 0.052 0.562
Tri 2 0.16 0.081 1.05 0.014 0.626
Age 1 0.30 0.296 3.85 0.026 0.450
Parity 1 0.12 0.119 1.55 0.010 0.914
BMI 1 0.23 0.226 2.93 0.020 0.963
BMI_Time_Interaction 1 0.08 0.083 1.08 0.007 0.155
Residuals 120 9.24 0.077 0.811 0.365
Total 133 11.39 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.2.4 BMI (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.33 0.165 2.14 0.029 0.432
T1Dstatus 1 0.34 0.340 4.42 0.030 0.043 *
seqRun 4 0.60 0.149 1.93 0.052 0.536
Tri 2 0.16 0.081 1.05 0.014 0.581
Age 1 0.30 0.296 3.85 0.026 0.445
Parity 1 0.12 0.119 1.55 0.010 0.935
BMI 1 0.23 0.226 2.93 0.020 0.956
Residuals 121 9.32 0.077 0.818 0.399
Total 133 11.39 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.3 HLA type
9.1.9.3.1 HLA type interaction with time (reference: DR34 )
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.33 0.165 2.15 0.029 0.396
T1Dstatus 1 0.34 0.340 4.43 0.030 0.054 .
Days 1 0.22 0.222 2.90 0.020 0.070 .
seqRun 4 0.55 0.138 1.80 0.048 0.648
Age 1 0.28 0.282 3.68 0.025 0.469
Parity 1 0.12 0.122 1.58 0.011 0.929
BMI 1 0.21 0.210 2.73 0.018 0.972
HLA_Time_Interaction 1 0.05 0.046 0.60 0.004 0.996
Residuals 121 9.29 0.077 0.815 0.359
Total 133 11.39 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.3.2 HLA type interaction with time (reference: DRXX)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.33 0.165 2.16 0.029 0.425
T1Dstatus 1 0.34 0.340 4.44 0.030 0.051 .
Days 1 0.22 0.222 2.90 0.020 0.064 .
seqRun 4 0.55 0.138 1.80 0.048 0.630
Age 1 0.28 0.282 3.69 0.025 0.460
Parity 1 0.12 0.122 1.59 0.011 0.924
BMI 1 0.21 0.210 2.74 0.018 0.972
HLA_Time_Interaction 1 0.07 0.069 0.89 0.006 0.997
Residuals 121 9.27 0.077 0.813 0.462
Total 133 11.39 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.3.3 HLA type interaction with time (reference: Group3o4)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.33 0.165 2.15 0.029 0.392
T1Dstatus 1 0.34 0.340 4.43 0.030 0.048 *
Days 1 0.22 0.222 2.90 0.020 0.064 .
seqRun 4 0.55 0.138 1.79 0.048 0.596
Age 1 0.28 0.282 3.68 0.025 0.466
Parity 1 0.12 0.122 1.58 0.011 0.932
BMI 1 0.21 0.210 2.73 0.018 0.971
HLA_Time_Interaction 1 0.04 0.041 0.53 0.004 0.277
Residuals 121 9.29 0.077 0.816 0.231
Total 133 11.39 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.3.4 HLA type (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
Days 1 0.24 0.2376 3.10 0.021 0.046 *
seqRun 4 0.51 0.1283 1.68 0.045 0.840
Age 1 0.28 0.2783 3.64 0.024 0.840
Parity 1 0.18 0.1780 2.33 0.016 0.005 **
BMI 1 0.29 0.2901 3.79 0.025 0.981
T1Dstatus 1 0.31 0.3095 4.04 0.027 0.052 .
HLA 2 0.25 0.1254 1.64 0.022 0.616
Residuals 122 9.33 0.0765 0.819 0.261
Total 133 11.39 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.3.5 HLA (no interaction: T1)
Call:
adonis(formula = D ~ SeqRun + Nulliparous + BMI_conception + T1Dstatus + Age_LMP + HLA.6DRML, data = Meta_df)
Permutation: free
Number of permutations: 999
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
SeqRun 3 0.240 0.0800 0.901 0.118 0.588
Nulliparous 1 0.162 0.1622 1.827 0.080 0.089 .
BMI_conception 1 0.088 0.0875 0.985 0.043 0.410
T1Dstatus 1 0.180 0.1797 2.024 0.089 0.075 .
Age_LMP 1 0.071 0.0712 0.802 0.035 0.598
HLA.6DRML 2 0.134 0.0668 0.753 0.066 0.694
Residuals 13 1.154 0.0888 0.569
Total 22 2.029 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.3.6 HLA type (no interaction: T2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
Days 1 0.14 0.1431 2.035 0.040 0.596
seqRun 3 0.53 0.1751 2.490 0.149 0.519
Age 1 0.12 0.1224 1.741 0.035 0.703
Parity 1 0.10 0.1020 1.451 0.029 0.786
BMI 1 0.08 0.0815 1.159 0.023 0.901
T1Dstatus 1 0.17 0.1723 2.451 0.049 0.058 .
HLA 2 0.14 0.0697 0.992 0.039 0.595
Residuals 32 2.25 0.0703 0.636 0.300
Total 42 3.54 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.3.7 HLA type (no interaction: T3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
Days 1 0.20 0.1954 2.39 0.035 0.678
seqRun 4 0.22 0.0553 0.67 0.039 0.528
Age 1 0.08 0.0841 1.03 0.015 0.197
Parity 1 0.16 0.1570 1.92 0.028 0.016 *
BMI 1 0.26 0.2617 3.20 0.046 0.914
T1Dstatus 1 0.09 0.0921 1.12 0.016 0.333
HLA 2 0.04 0.0222 0.27 0.008 0.997
Residuals 56 4.58 0.0819 0.813 0.937
Total 67 5.64 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.4 Parity
9.1.9.4.1 Parity interaction with time
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.33 0.165 2.17 0.029 0.429
T1Dstatus 1 0.34 0.340 4.47 0.030 0.051 .
Days 1 0.22 0.222 2.92 0.020 0.082 .
seqRun 4 0.55 0.138 1.81 0.048 0.629
Age 1 0.28 0.282 3.71 0.025 0.437
Parity 1 0.12 0.122 1.60 0.011 0.925
BMI 1 0.21 0.210 2.75 0.018 0.966
Parity_Time_Interaction 1 0.12 0.120 1.58 0.011 0.051 .
Residuals 121 9.21 0.076 0.809 0.159
Total 133 11.39 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.4.2 Parity (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.33 0.165 2.16 0.029 0.382
T1Dstatus 1 0.34 0.340 4.45 0.030 0.058 .
Days 1 0.22 0.222 2.91 0.020 0.061 .
seqRun 4 0.55 0.138 1.80 0.048 0.634
BMI 1 0.22 0.216 2.83 0.019 0.961
Age 1 0.28 0.280 3.66 0.025 0.486
Parity 1 0.12 0.118 1.54 0.010 0.970
Residuals 122 9.33 0.077 0.819 0.253
Total 133 11.39 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.4.3 Parity (no interaction but within T1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.222 0.1112 1.304 0.110 0.27
T1Dstatus 1 0.071 0.0706 0.828 0.035 0.63
seqRun 1 0.166 0.1662 1.950 0.082 0.26
Age 1 0.110 0.1100 1.291 0.054 0.78
BMI 1 0.066 0.0661 0.775 0.033 0.78
Parity 1 0.114 0.1143 1.340 0.056 0.49
Residuals 15 1.279 0.0853 0.630 0.52
Total 22 2.029 1.000 9.1.9.4.4 Parity (no interaction but within T2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.21 0.1048 1.386 0.059 0.441
T1Dstatus 1 0.22 0.2228 2.947 0.063 0.067 .
seqRun 1 0.16 0.1552 2.053 0.044 0.801
Age 1 0.14 0.1408 1.863 0.040 0.161
BMI 1 0.10 0.1010 1.336 0.029 0.235
Parity 1 0.06 0.0612 0.809 0.017 0.732
Residuals 35 2.65 0.0756 0.748 0.162
Total 42 3.54 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.4.5 Parity (no interaction but within T3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.09 0.0432 0.526 0.015 0.935
T1Dstatus 1 0.18 0.1834 2.233 0.033 0.047 *
seqRun 1 0.03 0.0254 0.310 0.005 0.046 *
Age 1 0.11 0.1055 1.284 0.019 0.693
BMI 1 0.16 0.1599 1.946 0.028 0.970
Parity 1 0.15 0.1491 1.815 0.026 0.894
Residuals 60 4.93 0.0822 0.874 0.782
Total 67 5.64 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.5 Mode of delivery
9.1.9.5.1 Mode of delivery interaction with time (reference: Emergency caesarea)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.33 0.165 2.20 0.029 0.412
T1Dstatus 1 0.34 0.340 4.53 0.030 0.050 *
MOD 2 0.26 0.130 1.73 0.023 0.641
Days 1 0.23 0.226 3.01 0.020 0.055 .
seqRun 4 0.54 0.134 1.79 0.047 0.654
Age 1 0.42 0.417 5.56 0.037 0.007 **
Parity 1 0.14 0.139 1.85 0.012 0.639
BMI 1 0.18 0.184 2.45 0.016 0.977
MOD_Time_Interaction 1 0.03 0.029 0.39 0.003 1.000
Residuals 119 8.93 0.075 0.784 0.341
Total 133 11.39 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.5.2 Mode of delivery interaction with time (reference: Elective caesarea)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.33 0.165 2.21 0.029 0.412
T1Dstatus 1 0.34 0.340 4.55 0.030 0.048 *
MOD 2 0.26 0.130 1.74 0.023 0.632
Days 1 0.23 0.226 3.02 0.020 0.052 .
seqRun 4 0.54 0.134 1.80 0.047 0.669
Age 1 0.42 0.417 5.58 0.037 0.009 **
Parity 1 0.14 0.139 1.86 0.012 0.684
BMI 1 0.18 0.184 2.46 0.016 0.970
MOD_Time_Interaction 1 0.06 0.059 0.78 0.005 1.000
Residuals 119 8.90 0.075 0.781 0.432
Total 133 11.39 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.5.3 Mode of delivery interaction with time (reference: Labour)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.33 0.165 2.20 0.029 0.422
T1Dstatus 1 0.34 0.340 4.54 0.030 0.054 .
MOD 2 0.26 0.130 1.73 0.023 0.639
Days 1 0.23 0.226 3.01 0.020 0.055 .
seqRun 4 0.54 0.134 1.79 0.047 0.630
Age 1 0.42 0.417 5.56 0.037 0.002 **
Parity 1 0.14 0.139 1.85 0.012 0.683
BMI 1 0.18 0.184 2.45 0.016 0.974
MOD_Time_Interaction 1 0.03 0.030 0.41 0.003 1.000
Residuals 119 8.93 0.075 0.784 0.525
Total 133 11.39 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.5.4 Mode of delivery (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
Days 1 0.24 0.2376 3.18 0.021 0.053 .
seqRun 4 0.51 0.1283 1.72 0.045 0.831
Age 1 0.28 0.2783 3.73 0.024 0.851
Parity 1 0.18 0.1780 2.38 0.016 0.005 **
BMI 1 0.29 0.2901 3.89 0.025 0.979
HLA 2 0.27 0.1340 1.80 0.024 0.581
T1Dstatus 1 0.29 0.2922 3.91 0.026 0.065 .
MOD 2 0.38 0.1884 2.52 0.033 0.208
Residuals 120 8.96 0.0747 0.786 0.192
Total 133 11.39 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.6 Carbohydrate intake
9.1.9.6.1 Carbohydrate interaction with time (reference: trimester 1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.33 0.164 2.13 0.029 0.428
T1Dstatus 1 0.32 0.318 4.13 0.028 0.062 .
Carbs 1 0.21 0.208 2.71 0.018 0.214
seqRun 4 0.58 0.146 1.90 0.052 0.626
Tri 2 0.17 0.087 1.13 0.015 0.445
Age 1 0.29 0.293 3.81 0.026 0.493
Parity 1 0.12 0.119 1.54 0.010 0.868
BMI 1 0.23 0.231 3.00 0.020 0.843
Carb_Time_Interaction 1 0.05 0.055 0.71 0.005 0.826
Residuals 117 9.00 0.077 0.796 0.371
Total 131 11.31 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.6.2 Carbohydrate interaction with time (reference: trimester 2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.33 0.164 2.13 0.029 0.431
T1Dstatus 1 0.32 0.318 4.13 0.028 0.063 .
Carbs 1 0.21 0.208 2.70 0.018 0.202
seqRun 4 0.58 0.146 1.89 0.052 0.647
Tri 2 0.17 0.087 1.13 0.015 0.432
Age 1 0.29 0.293 3.80 0.026 0.503
Parity 1 0.12 0.119 1.54 0.010 0.867
BMI 1 0.23 0.231 2.99 0.020 0.852
Carb_Time_Interaction 1 0.04 0.042 0.54 0.004 0.963
Residuals 117 9.02 0.077 0.797 0.423
Total 131 11.31 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.6.3 Carbohydrate interaction with time (reference: trimester 3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.33 0.164 2.13 0.029 0.445
T1Dstatus 1 0.32 0.318 4.13 0.028 0.076 .
Carbs 1 0.21 0.208 2.71 0.018 0.246
seqRun 4 0.58 0.146 1.89 0.052 0.628
Tri 2 0.17 0.087 1.13 0.015 0.438
Age 1 0.29 0.293 3.81 0.026 0.510
Parity 1 0.12 0.119 1.54 0.010 0.868
BMI 1 0.23 0.231 3.00 0.020 0.836
Carb_Time_Interaction 1 0.05 0.047 0.62 0.004 0.921
Residuals 117 9.01 0.077 0.796 0.441
Total 131 11.31 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.6.4 Carbohydrate (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 0.58 0.1444 1.88 0.051 0.693
Tri 2 0.17 0.0851 1.11 0.015 0.517
Age 1 0.30 0.3020 3.93 0.027 0.703
Parity 1 0.17 0.1664 2.17 0.015 0.008 **
BMI 1 0.27 0.2696 3.51 0.024 0.975
HLA 2 0.27 0.1334 1.74 0.024 0.587
T1Dstatus 1 0.28 0.2830 3.69 0.025 0.059 .
Carbs 1 0.22 0.2187 2.85 0.019 0.162
Residuals 118 9.06 0.0768 0.801 0.281
Total 131 11.31 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.7 Fibre intake
9.1.9.7.1 Fibre interaction with time (reference: trimester 1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.33 0.164 2.11 0.029 0.456
T1Dstatus 1 0.32 0.318 4.09 0.028 0.048 *
Fiber 1 0.12 0.123 1.58 0.011 0.630
seqRun 4 0.59 0.146 1.88 0.052 0.589
Tri 2 0.17 0.086 1.11 0.015 0.422
Age 1 0.31 0.309 3.97 0.027 0.350
Parity 1 0.12 0.118 1.52 0.010 0.866
BMI 1 0.21 0.212 2.72 0.019 0.911
Fiber_Time_Interaction 1 0.05 0.051 0.65 0.004 0.456
Residuals 117 9.10 0.078 0.804 0.466
Total 131 11.31 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.7.2 Fibre interaction with time (reference: trimester 2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.33 0.164 2.10 0.029 0.411
T1Dstatus 1 0.32 0.318 4.08 0.028 0.072 .
Fiber 1 0.12 0.123 1.58 0.011 0.612
seqRun 4 0.59 0.146 1.88 0.052 0.616
Tri 2 0.17 0.086 1.11 0.015 0.445
Age 1 0.31 0.309 3.96 0.027 0.348
Parity 1 0.12 0.118 1.51 0.010 0.876
BMI 1 0.21 0.212 2.72 0.019 0.901
Fiber_Time_Interaction 1 0.02 0.025 0.32 0.002 0.866
Residuals 117 9.12 0.078 0.806 0.544
Total 131 11.31 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.7.3 Fibre interaction with time (reference: trimester 3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.33 0.164 2.12 0.029 0.457
T1Dstatus 1 0.32 0.318 4.11 0.028 0.066 .
Fiber 1 0.12 0.123 1.59 0.011 0.576
seqRun 4 0.59 0.146 1.89 0.052 0.631
Tri 2 0.17 0.086 1.11 0.015 0.433
Age 1 0.31 0.309 3.99 0.027 0.333
Parity 1 0.12 0.118 1.52 0.010 0.883
BMI 1 0.21 0.212 2.74 0.019 0.907
Fiber_Time_Interaction 1 0.09 0.086 1.11 0.008 0.512
Residuals 117 9.06 0.077 0.801 0.489
Total 131 11.31 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.7.4 Fibre (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 0.58 0.1444 1.86 0.051 0.633
Tri 2 0.17 0.0851 1.10 0.015 0.504
Age 1 0.30 0.3020 3.90 0.027 0.701
Parity 1 0.17 0.1664 2.15 0.015 0.021 *
BMI 1 0.27 0.2696 3.48 0.024 0.978
HLA 2 0.27 0.1334 1.72 0.024 0.543
T1Dstatus 1 0.28 0.2830 3.65 0.025 0.065 .
Fiber 1 0.13 0.1297 1.67 0.011 0.482
Residuals 118 9.15 0.0775 0.809 0.457
Total 131 11.31 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.8 1,5-AG (glucose control measurement)
9.1.9.8.1 1,5-AG interaction with time
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.33 0.164 2.20 0.034 0.457
T1Dstatus 1 0.44 0.441 5.92 0.045 0.018 *
Days 1 0.13 0.129 1.73 0.013 0.297
seqRun 3 0.46 0.152 2.04 0.047 0.915
Age 1 0.33 0.330 4.44 0.034 0.073 .
Parity 1 0.12 0.118 1.58 0.012 0.941
BMI 1 0.13 0.128 1.72 0.013 0.986
AG15 1 0.22 0.223 2.99 0.023 0.007 **
AG15_T1D_Interaction 1 0.13 0.133 1.78 0.014 0.621
Residuals 100 7.45 0.074 0.765 0.075 .
Total 112 9.73 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.8.2 1,5-AG within T1D women
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.19 0.0944 1.70 0.053 0.680
Days 1 0.11 0.1075 1.93 0.030 0.165
seqRun 3 0.44 0.1478 2.66 0.125 0.825
Age 1 0.16 0.1570 2.83 0.044 0.069 .
Parity 1 0.13 0.1310 2.36 0.037 0.137
BMI 1 0.23 0.2272 4.09 0.064 0.182
AG15 1 0.13 0.1324 2.38 0.037 0.647
Residuals 39 2.17 0.0555 0.610 0.392
Total 49 3.55 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 19.1.9.8.3 1,5-AG interaction with time (within non-T1D women)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.43 0.2141 2.63 0.074 0.26
Days 1 0.09 0.0889 1.09 0.015 0.44
seqRun 3 0.36 0.1213 1.49 0.063 0.87
Age 1 0.31 0.3140 3.86 0.055 0.19
Parity 1 0.07 0.0652 0.80 0.011 0.98
BMI 1 0.05 0.0502 0.62 0.009 1.00
AG15 1 0.22 0.2166 2.66 0.038 0.75
Residuals 52 4.23 0.0814 0.735 0.78
Total 62 5.76 1.000 10 Order taxonomic level
10.1 Microbial community composition analysis at Order level (Beta diversity analysis)
10.1.1 Interaction between T1D status and Time
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 0.21 0.0535 1.65 0.045 0.519
Days 1 0.04 0.0362 1.12 0.008 0.599
T1D_Time_Interaction 1 0.28 0.2766 8.53 0.058 0.039 *
Age 1 0.06 0.0619 1.91 0.013 0.637
Parity 1 0.08 0.0798 2.46 0.017 0.487
BMI 1 0.07 0.0700 2.16 0.015 0.767
HLA 2 0.07 0.0348 1.07 0.015 0.673
T1Dstatus 1 0.02 0.0240 0.74 0.005 0.675
Residuals 121 3.92 0.0324 0.825 0.671
Total 133 4.76 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1[1] 0.03910.1.2 T1D status in trimester 1
Call:
adonis(formula = D ~ SeqRun + Nulliparous + Age_LMP + BMI_conception + HLA.6DRML + T1Dstatus, data = Meta_dfTri)
Permutation: free
Number of permutations: 999
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
SeqRun 3 0.107 0.0356 1.07 0.120 0.381
Nulliparous 1 0.200 0.1999 6.00 0.225 0.011 *
Age_LMP 1 0.022 0.0220 0.66 0.025 0.514
BMI_conception 1 0.009 0.0088 0.26 0.010 0.843
HLA.6DRML 2 0.049 0.0244 0.73 0.055 0.566
T1Dstatus 1 0.068 0.0681 2.04 0.077 0.133
Residuals 13 0.433 0.0333 0.488
Total 22 0.888 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1[1] 0.133Beta diversity Plot
10.1.3 T1D status in trimester 2
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 3 0.303 0.1010 2.699 0.171 0.001 ***
Age 1 0.028 0.0283 0.757 0.016 0.484
Parity 1 0.029 0.0288 0.769 0.016 0.173
BMI 1 0.039 0.0390 1.043 0.022 0.359
HLA 2 0.040 0.0202 0.539 0.023 0.748
T1Dstatus 1 0.096 0.0959 2.564 0.054 0.123
Residuals 33 1.235 0.0374 0.698 0.384
Total 42 1.770 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
10.1.4 T1D status in trimester 3
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 0.093 0.0234 0.84 0.046 0.796
Age 1 0.019 0.0187 0.67 0.009 0.821
Parity 1 0.122 0.1217 4.37 0.060 0.822
BMI 1 0.113 0.1130 4.06 0.055 0.461
HLA 2 0.035 0.0176 0.63 0.017 0.635
T1Dstatus 1 0.075 0.0748 2.69 0.037 0.077 .
Residuals 57 1.587 0.0278 0.776 0.292
Total 67 2.044 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
10.1.5 Days within T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.062 0.0309 1.64 0.038
seqRun 3 0.194 0.0647 3.44 0.121
Age 1 0.025 0.0253 1.34 0.016
Parity 1 0.104 0.1036 5.50 0.064
BMI 1 0.072 0.0722 3.84 0.045
Days 1 0.060 0.0596 3.17 0.037
Residuals 58 1.091 0.0188 0.679
Total 67 1.608 1.000 Beta diversity Plot
10.1.6 Trimester within T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.062 0.0309 1.64 0.038 0.54
seqRun 3 0.194 0.0647 3.43 0.121 0.68
Age 1 0.025 0.0253 1.34 0.016 0.78
Parity 1 0.104 0.1036 5.50 0.064 0.14
BMI 1 0.072 0.0722 3.83 0.045 0.43
Tri 2 0.077 0.0384 2.04 0.048 0.14
Residuals 57 1.074 0.0188 0.668 0.27
Total 67 1.608 1.000 Beta diversity Plot
10.1.7 Days within non-T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.214 0.1069 2.55 0.074 0.289
seqRun 4 0.119 0.0297 0.71 0.041 0.865
Age 1 0.196 0.1964 4.68 0.068 0.025 *
Parity 1 0.032 0.0316 0.75 0.011 0.780
BMI 1 0.007 0.0069 0.16 0.002 0.993
Days 1 0.016 0.0157 0.38 0.005 0.712
Residuals 55 2.305 0.0419 0.798 0.319
Total 65 2.888 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
10.1.8 Trimester within non-T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.214 0.1069 2.56 0.074 0.277
seqRun 4 0.119 0.0297 0.71 0.041 0.885
Age 1 0.196 0.1964 4.71 0.068 0.026 *
Parity 1 0.032 0.0316 0.76 0.011 0.804
BMI 1 0.007 0.0069 0.17 0.002 0.994
Tri 2 0.069 0.0346 0.83 0.024 0.808
Residuals 54 2.252 0.0417 0.780 0.434
Total 65 2.888 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
10.1.9 Other factors
10.1.9.1 Age at conception
10.1.9.1.1 Age at conception interaction with time (reference: trimester 1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.10 0.0509 1.57 0.021 0.540
T1Dstatus 1 0.22 0.2230 6.89 0.047 0.043 *
seqRun 4 0.24 0.0606 1.87 0.051 0.183
Tri 2 0.08 0.0376 1.16 0.016 0.794
Age 1 0.07 0.0706 2.18 0.015 0.465
Parity 1 0.07 0.0733 2.26 0.015 0.786
BMI 1 0.06 0.0595 1.84 0.013 0.945
Age_Time_Interaction 1 0.03 0.0272 0.84 0.006 0.299
Residuals 120 3.88 0.0324 0.816 0.340
Total 133 4.76 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.1.2 Age at conception interaction with time (reference: trimester 2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.10 0.0509 1.56 0.021 0.540
T1Dstatus 1 0.22 0.2230 6.85 0.047 0.055 .
seqRun 4 0.24 0.0606 1.86 0.051 0.186
Tri 2 0.08 0.0376 1.16 0.016 0.790
Age 1 0.07 0.0706 2.17 0.015 0.459
Parity 1 0.07 0.0733 2.25 0.015 0.797
BMI 1 0.06 0.0595 1.83 0.013 0.962
Age_Time_Interaction 1 0.00 0.0049 0.15 0.001 0.830
Residuals 120 3.90 0.0325 0.821 0.399
Total 133 4.76 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.1.3 Age at conception interaction with time (reference: trimester 3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.10 0.0509 1.57 0.021 0.548
T1Dstatus 1 0.22 0.2230 6.90 0.047 0.053 .
seqRun 4 0.24 0.0606 1.87 0.051 0.188
Tri 2 0.08 0.0376 1.16 0.016 0.801
Age 1 0.07 0.0706 2.19 0.015 0.493
Parity 1 0.07 0.0733 2.27 0.015 0.784
BMI 1 0.06 0.0595 1.84 0.013 0.945
Age_Time_Interaction 1 0.03 0.0325 1.01 0.007 0.136
Residuals 120 3.88 0.0323 0.815 0.308
Total 133 4.76 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.1.4 Age at conception (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.10 0.0509 1.57 0.021 0.526
T1Dstatus 1 0.22 0.2230 6.90 0.047 0.051 .
seqRun 4 0.24 0.0606 1.87 0.051 0.211
Tri 2 0.08 0.0376 1.16 0.016 0.799
Parity 1 0.07 0.0737 2.28 0.016 0.830
BMI 1 0.06 0.0557 1.72 0.012 0.961
Age 1 0.07 0.0740 2.29 0.016 0.509
Residuals 121 3.91 0.0323 0.822 0.360
Total 133 4.76 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.2 Body max index (BMI)
10.1.9.2.1 BMI interaction with time (reference: trimester 1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.10 0.0509 1.57 0.021 0.547
T1Dstatus 1 0.22 0.2230 6.86 0.047 0.059 .
seqRun 4 0.24 0.0606 1.86 0.051 0.208
Tri 2 0.08 0.0376 1.16 0.016 0.801
Age 1 0.07 0.0706 2.17 0.015 0.471
Parity 1 0.07 0.0733 2.26 0.015 0.783
BMI 1 0.06 0.0595 1.83 0.013 0.952
BMI_Time_Interaction 1 0.01 0.0114 0.35 0.002 0.699
Residuals 120 3.90 0.0325 0.820 0.438
Total 133 4.76 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.2.2 BMI interaction with time (reference: trimester 2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.10 0.0509 1.56 0.021 0.523
T1Dstatus 1 0.22 0.2230 6.84 0.047 0.055 .
seqRun 4 0.24 0.0606 1.86 0.051 0.197
Tri 2 0.08 0.0376 1.15 0.016 0.822
Age 1 0.07 0.0706 2.17 0.015 0.491
Parity 1 0.07 0.0733 2.25 0.015 0.783
BMI 1 0.06 0.0595 1.83 0.013 0.939
BMI_Time_Interaction 1 0.00 -0.0034 -0.10 -0.001 0.959
Residuals 120 3.91 0.0326 0.823 0.417
Total 133 4.76 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.2.3 BMI interaction with time (reference: trimester 3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.10 0.0509 1.57 0.021 0.552
T1Dstatus 1 0.22 0.2230 6.86 0.047 0.048 *
seqRun 4 0.24 0.0606 1.86 0.051 0.179
Tri 2 0.08 0.0376 1.16 0.016 0.807
Age 1 0.07 0.0706 2.17 0.015 0.473
Parity 1 0.07 0.0733 2.25 0.015 0.804
BMI 1 0.06 0.0595 1.83 0.013 0.954
BMI_Time_Interaction 1 0.01 0.0092 0.28 0.002 0.613
Residuals 120 3.90 0.0325 0.820 0.376
Total 133 4.76 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.2.4 BMI (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.10 0.0509 1.57 0.021 0.541
T1Dstatus 1 0.22 0.2230 6.90 0.047 0.044 *
seqRun 4 0.24 0.0606 1.87 0.051 0.176
Tri 2 0.08 0.0376 1.16 0.016 0.782
Age 1 0.07 0.0706 2.19 0.015 0.477
Parity 1 0.07 0.0733 2.27 0.015 0.768
BMI 1 0.06 0.0595 1.84 0.013 0.949
Residuals 121 3.91 0.0323 0.822 0.357
Total 133 4.76 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.3 HLA type
10.1.9.3.1 HLA type interaction with time (reference: DR34 )
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.10 0.0509 1.56 0.021 0.522
T1Dstatus 1 0.22 0.2230 6.86 0.047 0.052 .
Days 1 0.01 0.0111 0.34 0.002 0.889
seqRun 4 0.26 0.0653 2.01 0.055 0.244
Age 1 0.07 0.0684 2.10 0.014 0.425
Parity 1 0.08 0.0758 2.33 0.016 0.778
BMI 1 0.06 0.0564 1.73 0.012 0.943
HLA_Time_Interaction 1 0.02 0.0219 0.67 0.005 0.678
Residuals 121 3.94 0.0325 0.828 0.270
Total 133 4.76 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.3.2 HLA type interaction with time (reference: DRXX)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.10 0.0509 1.56 0.021 0.55
T1Dstatus 1 0.22 0.2230 6.85 0.047 0.04 *
Days 1 0.01 0.0111 0.34 0.002 0.89
seqRun 4 0.26 0.0653 2.00 0.055 0.27
Age 1 0.07 0.0684 2.10 0.014 0.46
Parity 1 0.08 0.0758 2.33 0.016 0.74
BMI 1 0.06 0.0564 1.73 0.012 0.95
HLA_Time_Interaction 1 0.02 0.0176 0.54 0.004 1.00
Residuals 121 3.94 0.0326 0.829 0.54
Total 133 4.76 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.3.3 HLA type interaction with time (reference: Group3o4)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.10 0.0509 1.56 0.021 0.539
T1Dstatus 1 0.22 0.2230 6.82 0.047 0.045 *
Days 1 0.01 0.0111 0.34 0.002 0.909
seqRun 4 0.26 0.0653 2.00 0.055 0.237
Age 1 0.07 0.0684 2.09 0.014 0.430
Parity 1 0.08 0.0758 2.32 0.016 0.764
BMI 1 0.06 0.0564 1.72 0.012 0.950
HLA_Time_Interaction 1 0.00 0.0026 0.08 0.001 0.939
Residuals 121 3.96 0.0327 0.832 0.289
Total 133 4.76 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.3.4 HLA type (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
Days 1 0.02 0.0167 0.52 0.004 0.76
seqRun 4 0.23 0.0584 1.80 0.049 0.65
Age 1 0.06 0.0646 1.99 0.014 0.64
Parity 1 0.09 0.0927 2.86 0.020 0.33
BMI 1 0.11 0.1073 3.31 0.023 0.31
T1Dstatus 1 0.21 0.2119 6.53 0.045 0.05 *
HLA 2 0.07 0.0354 1.09 0.015 0.69
Residuals 122 3.96 0.0324 0.832 0.28
Total 133 4.76 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.4 Parity
10.1.9.4.1 Parity interaction with time
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.10 0.0509 1.61 0.021 0.538
T1Dstatus 1 0.22 0.2230 7.05 0.047 0.042 *
Days 1 0.01 0.0111 0.35 0.002 0.895
seqRun 4 0.26 0.0653 2.06 0.055 0.260
Age 1 0.07 0.0684 2.16 0.014 0.422
Parity 1 0.08 0.0758 2.40 0.016 0.766
BMI 1 0.06 0.0564 1.78 0.012 0.929
Parity_Time_Interaction 1 0.13 0.1305 4.12 0.027 0.043 *
Residuals 121 3.83 0.0316 0.805 0.122
Total 133 4.76 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.4.2 Parity (no interaction but within T1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.053 0.0263 0.69 0.059 0.633
T1Dstatus 1 0.011 0.0107 0.28 0.012 0.860
seqRun 1 0.074 0.0744 1.95 0.084 0.045 *
Age 1 0.036 0.0359 0.94 0.040 0.721
BMI 1 0.016 0.0160 0.42 0.018 0.751
Parity 1 0.126 0.1261 3.31 0.142 0.405
Residuals 15 0.572 0.0381 0.644 0.736
Total 22 0.888 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.4.3 Parity (no interaction but within T2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.051 0.0253 0.63 0.029 0.725
T1Dstatus 1 0.173 0.1729 4.34 0.098 0.056 .
seqRun 1 0.078 0.0784 1.97 0.044 0.914
Age 1 0.032 0.0318 0.80 0.018 0.251
BMI 1 0.015 0.0151 0.38 0.009 0.478
Parity 1 0.026 0.0255 0.64 0.014 0.868
Residuals 35 1.396 0.0399 0.788 0.491
Total 42 1.770 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.4.4 Parity (no interaction but within T3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.045 0.0223 0.79 0.022 0.59
T1Dstatus 1 0.106 0.1057 3.73 0.052 0.06 .
seqRun 1 0.005 0.0052 0.18 0.003 0.06 .
Age 1 0.016 0.0161 0.57 0.008 0.76
BMI 1 0.024 0.0241 0.85 0.012 0.88
Parity 1 0.146 0.1464 5.16 0.072 0.79
Residuals 60 1.701 0.0284 0.833 0.30
Total 67 2.044 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.5 Mode of delivery
10.1.9.5.1 Mode of delivery interaction with time (reference: Emergency caesarea)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.10 0.0509 1.56 0.021 0.540
T1Dstatus 1 0.22 0.2230 6.84 0.047 0.054 .
MOD 2 0.08 0.0412 1.26 0.017 0.630
Days 1 0.01 0.0105 0.32 0.002 0.890
seqRun 4 0.22 0.0556 1.70 0.047 0.470
Age 1 0.09 0.0890 2.73 0.019 0.214
Parity 1 0.08 0.0786 2.41 0.017 0.599
BMI 1 0.05 0.0455 1.39 0.010 0.948
MOD_Time_Interaction 1 0.02 0.0209 0.64 0.004 0.982
Residuals 119 3.88 0.0326 0.816 0.669
Total 133 4.76 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.5.2 Mode of delivery interaction with time (reference: Elective caesarea)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.10 0.0509 1.57 0.021 0.555
T1Dstatus 1 0.22 0.2230 6.87 0.047 0.039 *
MOD 2 0.08 0.0412 1.27 0.017 0.624
Days 1 0.01 0.0105 0.32 0.002 0.898
seqRun 4 0.22 0.0556 1.71 0.047 0.485
Age 1 0.09 0.0890 2.74 0.019 0.204
Parity 1 0.08 0.0786 2.42 0.017 0.610
BMI 1 0.05 0.0455 1.40 0.010 0.945
MOD_Time_Interaction 1 0.04 0.0416 1.28 0.009 0.040 *
Residuals 119 3.86 0.0324 0.812 0.407
Total 133 4.76 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.5.3 Mode of delivery interaction with time (reference: Labour)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.10 0.0509 1.56 0.021 0.563
T1Dstatus 1 0.22 0.2230 6.84 0.047 0.042 *
MOD 2 0.08 0.0412 1.26 0.017 0.651
Days 1 0.01 0.0105 0.32 0.002 0.902
seqRun 4 0.22 0.0556 1.71 0.047 0.480
Age 1 0.09 0.0890 2.73 0.019 0.203
Parity 1 0.08 0.0786 2.41 0.017 0.624
BMI 1 0.05 0.0455 1.40 0.010 0.934
MOD_Time_Interaction 1 0.02 0.0241 0.74 0.005 0.994
Residuals 119 3.88 0.0326 0.816 0.700
Total 133 4.76 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.5.4 Mode of delivery (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
Days 1 0.02 0.0167 0.51 0.004 0.780
seqRun 4 0.23 0.0584 1.80 0.049 0.637
Age 1 0.06 0.0646 1.99 0.014 0.638
Parity 1 0.09 0.0927 2.85 0.020 0.295
BMI 1 0.11 0.1073 3.30 0.023 0.323
HLA 2 0.11 0.0528 1.62 0.022 0.496
T1Dstatus 1 0.18 0.1770 5.44 0.037 0.074 .
MOD 2 0.06 0.0277 0.85 0.012 0.793
Residuals 120 3.90 0.0325 0.821 0.485
Total 133 4.76 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.5.5 Mode of delivery (no interaction: T1)
Call:
adonis(formula = D ~ SeqRun + Nulliparous + BMI_conception + T1Dstatus + Age_LMP + HLA.6DRML + MOD, data = Meta_df)
Permutation: free
Number of permutations: 999
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
SeqRun 3 0.107 0.0356 1.09 0.120 0.376
Nulliparous 1 0.200 0.1999 6.10 0.225 0.009 **
BMI_conception 1 0.011 0.0114 0.35 0.013 0.794
T1Dstatus 1 0.093 0.0929 2.83 0.105 0.069 .
Age_LMP 1 0.017 0.0165 0.50 0.019 0.631
HLA.6DRML 2 0.027 0.0133 0.41 0.030 0.848
MOD 2 0.072 0.0362 1.11 0.082 0.371
Residuals 11 0.361 0.0328 0.406
Total 22 0.888 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.5.6 Mode of delivery (no interaction: T2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
Days 1 0.057 0.0572 1.491 0.032 0.775
seqRun 3 0.279 0.0930 2.422 0.158 0.184
Age 1 0.031 0.0306 0.798 0.017 0.675
Parity 1 0.027 0.0273 0.710 0.015 0.215
BMI 1 0.065 0.0646 1.682 0.036 0.802
HLA 2 0.019 0.0096 0.250 0.011 0.951
T1Dstatus 1 0.114 0.1142 2.974 0.064 0.065 .
MOD 2 0.026 0.0132 0.344 0.015 0.912
Residuals 30 1.152 0.0384 0.651 0.743
Total 42 1.770 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.5.7 Mode of delivery (no interaction: T3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
Days 1 0.098 0.0985 3.51 0.048 0.001 ***
seqRun 4 0.081 0.0204 0.73 0.040 0.480
Age 1 0.015 0.0154 0.55 0.008 0.827
Parity 1 0.137 0.1365 4.87 0.067 0.235
BMI 1 0.105 0.1045 3.73 0.051 0.466
HLA 2 0.024 0.0122 0.43 0.012 0.795
T1Dstatus 1 0.037 0.0369 1.32 0.018 0.239
MOD 2 0.033 0.0166 0.59 0.016 0.663
Residuals 54 1.513 0.0280 0.740 0.667
Total 67 2.044 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.6 Carbohydrate intake
10.1.9.6.1 Carbohydrate interaction with time (reference: trimester 1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.10 0.0494 1.52 0.021 0.565
T1Dstatus 1 0.21 0.2101 6.47 0.044 0.056 .
Carbs 1 0.03 0.0278 0.86 0.006 0.678
seqRun 4 0.26 0.0660 2.03 0.056 0.193
Tri 2 0.08 0.0389 1.20 0.016 0.705
Age 1 0.10 0.1022 3.15 0.022 0.152
Parity 1 0.06 0.0645 1.99 0.014 0.716
BMI 1 0.06 0.0595 1.83 0.013 0.879
Carb_Time_Interaction 1 0.03 0.0271 0.83 0.006 0.800
Residuals 117 3.80 0.0325 0.803 0.475
Total 131 4.73 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.6.2 Carbohydrate interaction with time (reference: trimester 2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.10 0.0494 1.52 0.021 0.576
T1Dstatus 1 0.21 0.2101 6.45 0.044 0.055 .
Carbs 1 0.03 0.0278 0.85 0.006 0.679
seqRun 4 0.26 0.0660 2.03 0.056 0.172
Tri 2 0.08 0.0389 1.20 0.016 0.726
Age 1 0.10 0.1022 3.14 0.022 0.153
Parity 1 0.06 0.0645 1.98 0.014 0.761
BMI 1 0.06 0.0595 1.83 0.013 0.874
Carb_Time_Interaction 1 0.02 0.0159 0.49 0.003 0.874
Residuals 117 3.81 0.0326 0.805 0.458
Total 131 4.73 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.6.3 Carbohydrate interaction with time (reference: trimester 3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.10 0.0494 1.52 0.021 0.585
T1Dstatus 1 0.21 0.2101 6.45 0.044 0.066 .
Carbs 1 0.03 0.0278 0.85 0.006 0.679
seqRun 4 0.26 0.0660 2.03 0.056 0.185
Tri 2 0.08 0.0389 1.19 0.016 0.724
Age 1 0.10 0.1022 3.14 0.022 0.153
Parity 1 0.06 0.0645 1.98 0.014 0.751
BMI 1 0.06 0.0595 1.83 0.013 0.872
Carb_Time_Interaction 1 0.01 0.0128 0.39 0.003 0.824
Residuals 117 3.81 0.0326 0.806 0.434
Total 131 4.73 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.6.4 Carbohydrate (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 0.23 0.0582 1.80 0.049 0.53
Tri 2 0.09 0.0441 1.36 0.019 0.71
Age 1 0.07 0.0719 2.22 0.015 0.69
Parity 1 0.08 0.0798 2.46 0.017 0.37
BMI 1 0.10 0.0957 2.95 0.020 0.64
HLA 2 0.09 0.0470 1.45 0.020 0.54
T1Dstatus 1 0.17 0.1653 5.10 0.035 0.06 .
Carbs 1 0.08 0.0771 2.38 0.016 0.26
Residuals 118 3.82 0.0324 0.809 0.36
Total 131 4.73 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.7 Fibre intake
10.1.9.7.1 Fibre interaction with time (reference: trimester 1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.10 0.0494 1.50 0.021 0.555
T1Dstatus 1 0.21 0.2101 6.36 0.044 0.057 .
Fiber 1 0.01 0.0070 0.21 0.001 0.965
seqRun 4 0.25 0.0625 1.89 0.053 0.279
Tri 2 0.07 0.0371 1.12 0.016 0.733
Age 1 0.09 0.0897 2.72 0.019 0.259
Parity 1 0.07 0.0680 2.06 0.014 0.677
BMI 1 0.05 0.0531 1.61 0.011 0.916
Fiber_Time_Interaction 1 0.02 0.0151 0.46 0.003 0.577
Residuals 117 3.86 0.0330 0.817 0.530
Total 131 4.73 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.7.2 Fibre interaction with time (reference: trimester 2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.10 0.0494 1.49 0.021 0.578
T1Dstatus 1 0.21 0.2101 6.34 0.044 0.057 .
Fiber 1 0.01 0.0070 0.21 0.001 0.980
seqRun 4 0.25 0.0625 1.89 0.053 0.241
Tri 2 0.07 0.0371 1.12 0.016 0.755
Age 1 0.09 0.0897 2.71 0.019 0.251
Parity 1 0.07 0.0680 2.05 0.014 0.680
BMI 1 0.05 0.0531 1.60 0.011 0.901
Fiber_Time_Interaction 1 0.00 0.0027 0.08 0.001 0.919
Residuals 117 3.88 0.0331 0.820 0.576
Total 131 4.73 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.7.3 Fibre interaction with time (reference: trimester 3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.10 0.0494 1.49 0.021 0.593
T1Dstatus 1 0.21 0.2101 6.36 0.044 0.069 .
Fiber 1 0.01 0.0070 0.21 0.001 0.973
seqRun 4 0.25 0.0625 1.89 0.053 0.266
Tri 2 0.07 0.0371 1.12 0.016 0.740
Age 1 0.09 0.0897 2.72 0.019 0.261
Parity 1 0.07 0.0680 2.06 0.014 0.677
BMI 1 0.05 0.0531 1.61 0.011 0.898
Fiber_Time_Interaction 1 0.01 0.0139 0.42 0.003 0.511
Residuals 117 3.86 0.0330 0.817 0.573
Total 131 4.73 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.7.4 Fibre (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 0.23 0.0582 1.77 0.049 0.536
Tri 2 0.09 0.0441 1.34 0.019 0.720
Age 1 0.07 0.0719 2.19 0.015 0.681
Parity 1 0.08 0.0798 2.43 0.017 0.342
BMI 1 0.10 0.0957 2.91 0.020 0.606
HLA 2 0.09 0.0470 1.43 0.020 0.557
T1Dstatus 1 0.17 0.1653 5.03 0.035 0.078 .
Fiber 1 0.02 0.0230 0.70 0.005 0.723
Residuals 118 3.88 0.0329 0.820 0.504
Total 131 4.73 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.8 1,5-AG (glucose control measurement)
10.1.9.8.1 1,5-AG interaction with time
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.12 0.0622 1.96 0.031 0.469
T1Dstatus 1 0.26 0.2645 8.35 0.066 0.030 *
Days 1 0.01 0.0116 0.37 0.003 0.898
seqRun 3 0.17 0.0564 1.78 0.042 0.686
Age 1 0.09 0.0948 2.99 0.024 0.118
Parity 1 0.05 0.0492 1.55 0.012 0.812
BMI 1 0.02 0.0228 0.72 0.006 0.970
AG15 1 0.08 0.0835 2.64 0.021 0.028 *
AG15_T1D_Interaction 1 0.05 0.0459 1.45 0.011 0.717
Residuals 100 3.17 0.0317 0.785 0.168
Total 112 4.03 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.8.2 1,5-AG within T1D women
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.022 0.0112 0.61 0.020 0.957
Days 1 0.054 0.0537 2.92 0.048 0.047 *
seqRun 3 0.150 0.0502 2.73 0.135 0.296
Age 1 0.022 0.0221 1.20 0.020 0.352
Parity 1 0.064 0.0641 3.48 0.058 0.570
BMI 1 0.031 0.0305 1.66 0.027 0.285
AG15 1 0.050 0.0500 2.72 0.045 0.021 *
Residuals 39 0.718 0.0184 0.646 0.220
Total 49 1.111 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 110.1.9.8.3 1,5-AG interaction with time (within non-T1D women)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.173 0.0866 2.18 0.066 0.411
Days 1 0.013 0.0131 0.33 0.005 0.806
seqRun 3 0.100 0.0333 0.84 0.038 0.907
Age 1 0.150 0.1501 3.78 0.057 0.067 .
Parity 1 0.025 0.0254 0.64 0.010 0.902
BMI 1 0.012 0.0123 0.31 0.005 0.974
AG15 1 0.084 0.0838 2.11 0.032 0.806
Residuals 52 2.067 0.0397 0.787 0.799
Total 62 2.625 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111 Phylum taxonomic level
11.1 Microbial community composition analysis at Phylum level (Beta diversity analysis)
11.1.1 Interaction between T1D status and Time
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 0.19 0.0483 1.70 0.046 0.637
Days 1 0.03 0.0255 0.90 0.006 0.647
T1D_Time_Interaction 1 0.25 0.2509 8.85 0.060 0.059 .
Age 1 0.06 0.0580 2.05 0.014 0.620
Parity 1 0.08 0.0802 2.83 0.019 0.499
BMI 1 0.07 0.0675 2.38 0.016 0.692
HLA 2 0.05 0.0253 0.89 0.012 0.696
T1Dstatus 1 0.02 0.0209 0.74 0.005 0.629
Residuals 121 3.43 0.0284 0.821 0.689
Total 133 4.18 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1[1] 0.05911.1.2 T1D status in trimester 1
Call:
adonis(formula = D ~ SeqRun + Nulliparous + Age_LMP + BMI_conception + HLA.6DRML + T1Dstatus, data = Meta_dfTri)
Permutation: free
Number of permutations: 999
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
SeqRun 3 0.093 0.0309 1.05 0.116 0.401
Nulliparous 1 0.194 0.1940 6.58 0.242 0.007 **
Age_LMP 1 0.016 0.0158 0.54 0.020 0.576
BMI_conception 1 0.008 0.0082 0.28 0.010 0.799
HLA.6DRML 2 0.041 0.0207 0.70 0.052 0.593
T1Dstatus 1 0.066 0.0658 2.23 0.082 0.109
Residuals 13 0.383 0.0295 0.478
Total 22 0.801 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1[1] 0.109Beta diversity Plot
11.1.3 T1D status in trimester 2
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 3 0.272 0.0907 2.694 0.171 0.68
Age 1 0.028 0.0285 0.846 0.018 0.63
Parity 1 0.025 0.0246 0.732 0.016 0.29
BMI 1 0.036 0.0356 1.058 0.022 0.44
HLA 2 0.030 0.0148 0.441 0.019 0.80
T1Dstatus 1 0.088 0.0877 2.604 0.055 0.11
Residuals 33 1.111 0.0337 0.699 0.40
Total 42 1.589 1.000 Beta diversity Plot
11.1.4 T1D status in trimester 3
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 0.081 0.0202 0.87 0.046 0.485
Age 1 0.016 0.0160 0.69 0.009 0.374
Parity 1 0.116 0.1161 4.97 0.066 0.871
BMI 1 0.114 0.1144 4.90 0.065 0.387
HLA 2 0.028 0.0139 0.59 0.016 0.629
T1Dstatus 1 0.062 0.0617 2.64 0.035 0.086 .
Residuals 57 1.331 0.0233 0.761 0.320
Total 67 1.747 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
11.1.5 Days within T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.056 0.0282 1.86 0.042 0.437
seqRun 3 0.175 0.0584 3.86 0.131 0.710
Age 1 0.008 0.0077 0.51 0.006 0.924
Parity 1 0.107 0.1065 7.04 0.080 0.139
BMI 1 0.066 0.0656 4.33 0.049 0.455
Days 1 0.047 0.0467 3.08 0.035 0.075 .
Residuals 58 0.878 0.0151 0.657 0.208
Total 67 1.336 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
11.1.6 Trimester within T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.056 0.0282 1.87 0.042 0.44
seqRun 3 0.175 0.0584 3.86 0.131 0.71
Age 1 0.008 0.0077 0.51 0.006 0.93
Parity 1 0.107 0.1065 7.05 0.080 0.14
BMI 1 0.066 0.0656 4.34 0.049 0.43
Tri 2 0.063 0.0315 2.08 0.047 0.17
Residuals 57 0.862 0.0151 0.645 0.28
Total 67 1.336 1.000 Beta diversity Plot
11.1.7 Days within non-T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.191 0.0953 2.53 0.073 0.282
seqRun 4 0.106 0.0266 0.71 0.041 0.869
Age 1 0.188 0.1878 4.99 0.072 0.018 *
Parity 1 0.027 0.0267 0.71 0.010 0.873
BMI 1 0.007 0.0072 0.19 0.003 0.743
Days 1 0.013 0.0128 0.34 0.005 0.730
Residuals 55 2.071 0.0377 0.796 0.323
Total 65 2.603 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
11.1.8 Trimester within non-T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.191 0.0953 2.54 0.073 0.300
seqRun 4 0.106 0.0266 0.71 0.041 0.845
Age 1 0.188 0.1878 5.01 0.072 0.018 *
Parity 1 0.027 0.0267 0.71 0.010 0.874
BMI 1 0.007 0.0072 0.19 0.003 0.738
Tri 2 0.059 0.0297 0.79 0.023 0.843
Residuals 54 2.025 0.0375 0.778 0.446
Total 65 2.603 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
11.1.9 Other factors
11.1.9.1 Age at conception
11.1.9.1.1 Age at conception interaction with time (reference: trimester 1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.08 0.0423 1.49 0.020 0.568
T1Dstatus 1 0.20 0.2033 7.18 0.049 0.052 .
seqRun 4 0.22 0.0557 1.97 0.053 0.168
Tri 2 0.06 0.0308 1.09 0.015 0.816
Age 1 0.07 0.0666 2.35 0.016 0.450
Parity 1 0.07 0.0698 2.46 0.017 0.836
BMI 1 0.05 0.0530 1.87 0.013 0.954
Age_Time_Interaction 1 0.02 0.0185 0.65 0.004 0.403
Residuals 120 3.40 0.0283 0.813 0.427
Total 133 4.18 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.1.2 Age at conception interaction with time (reference: trimester 2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.08 0.0423 1.49 0.020 0.546
T1Dstatus 1 0.20 0.2033 7.16 0.049 0.063 .
seqRun 4 0.22 0.0557 1.96 0.053 0.167
Tri 2 0.06 0.0308 1.08 0.015 0.810
Age 1 0.07 0.0666 2.34 0.016 0.480
Parity 1 0.07 0.0698 2.46 0.017 0.839
BMI 1 0.05 0.0530 1.87 0.013 0.955
Age_Time_Interaction 1 0.01 0.0061 0.21 0.001 0.773
Residuals 120 3.41 0.0284 0.816 0.446
Total 133 4.18 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.1.3 Age at conception interaction with time (reference: trimester 3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.08 0.0423 1.50 0.020 0.542
T1Dstatus 1 0.20 0.2033 7.20 0.049 0.054 .
seqRun 4 0.22 0.0557 1.97 0.053 0.182
Tri 2 0.06 0.0308 1.09 0.015 0.820
Age 1 0.07 0.0666 2.36 0.016 0.445
Parity 1 0.07 0.0698 2.47 0.017 0.851
BMI 1 0.05 0.0530 1.88 0.013 0.956
Age_Time_Interaction 1 0.03 0.0292 1.03 0.007 0.126
Residuals 120 3.39 0.0282 0.811 0.363
Total 133 4.18 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.1.4 Age at conception (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.08 0.0423 1.50 0.020 0.526
T1Dstatus 1 0.20 0.2033 7.20 0.049 0.042 *
seqRun 4 0.22 0.0557 1.97 0.053 0.182
Tri 2 0.06 0.0308 1.09 0.015 0.809
Parity 1 0.07 0.0702 2.49 0.017 0.867
BMI 1 0.05 0.0490 1.74 0.012 0.951
Age 1 0.07 0.0702 2.49 0.017 0.498
Residuals 121 3.42 0.0282 0.818 0.382
Total 133 4.18 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.2 Body max index (BMI)
11.1.9.2.1 BMI interaction with time (reference: trimester 1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.08 0.0423 1.49 0.020 0.556
T1Dstatus 1 0.20 0.2033 7.17 0.049 0.045 *
seqRun 4 0.22 0.0557 1.97 0.053 0.185
Tri 2 0.06 0.0308 1.09 0.015 0.813
Age 1 0.07 0.0666 2.35 0.016 0.490
Parity 1 0.07 0.0698 2.46 0.017 0.838
BMI 1 0.05 0.0530 1.87 0.013 0.956
BMI_Time_Interaction 1 0.01 0.0136 0.48 0.003 0.582
Residuals 120 3.40 0.0284 0.814 0.444
Total 133 4.18 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.2.2 BMI interaction with time (reference: trimester 2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.08 0.0423 1.49 0.020 0.562
T1Dstatus 1 0.20 0.2033 7.14 0.049 0.037 *
seqRun 4 0.22 0.0557 1.96 0.053 0.180
Tri 2 0.06 0.0308 1.08 0.015 0.791
Age 1 0.07 0.0666 2.34 0.016 0.450
Parity 1 0.07 0.0698 2.45 0.017 0.840
BMI 1 0.05 0.0530 1.86 0.013 0.952
BMI_Time_Interaction 1 0.00 -0.0010 -0.03 0.000 0.925
Residuals 120 3.42 0.0285 0.818 0.415
Total 133 4.18 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.2.3 BMI interaction with time (reference: trimester 3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.08 0.0423 1.49 0.020 0.546
T1Dstatus 1 0.20 0.2033 7.16 0.049 0.042 *
seqRun 4 0.22 0.0557 1.96 0.053 0.186
Tri 2 0.06 0.0308 1.08 0.015 0.804
Age 1 0.07 0.0666 2.35 0.016 0.468
Parity 1 0.07 0.0698 2.46 0.017 0.834
BMI 1 0.05 0.0530 1.87 0.013 0.944
BMI_Time_Interaction 1 0.01 0.0072 0.25 0.002 0.668
Residuals 120 3.41 0.0284 0.816 0.407
Total 133 4.18 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.2.4 BMI (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.08 0.0423 1.50 0.020 0.554
T1Dstatus 1 0.20 0.2033 7.20 0.049 0.047 *
seqRun 4 0.22 0.0557 1.97 0.053 0.169
Tri 2 0.06 0.0308 1.09 0.015 0.818
Age 1 0.07 0.0666 2.36 0.016 0.477
Parity 1 0.07 0.0698 2.47 0.017 0.848
BMI 1 0.05 0.0530 1.88 0.013 0.962
Residuals 121 3.42 0.0282 0.818 0.416
Total 133 4.18 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.3 HLA type
11.1.9.3.1 HLA type interaction with time (reference: DR34 )
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.08 0.0423 1.49 0.020 0.579
T1Dstatus 1 0.20 0.2033 7.14 0.049 0.042 *
Days 1 0.01 0.0054 0.19 0.001 0.944
seqRun 4 0.24 0.0595 2.09 0.057 0.246
Age 1 0.06 0.0643 2.26 0.015 0.418
Parity 1 0.07 0.0724 2.54 0.017 0.826
BMI 1 0.05 0.0501 1.76 0.012 0.952
HLA_Time_Interaction 1 0.01 0.0141 0.49 0.003 0.608
Residuals 121 3.45 0.0285 0.825 0.329
Total 133 4.18 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.3.2 HLA type interaction with time (reference: DRXX)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.08 0.0423 1.49 0.020 0.565
T1Dstatus 1 0.20 0.2033 7.14 0.049 0.051 .
Days 1 0.01 0.0054 0.19 0.001 0.951
seqRun 4 0.24 0.0595 2.09 0.057 0.247
Age 1 0.06 0.0643 2.26 0.015 0.417
Parity 1 0.07 0.0724 2.54 0.017 0.813
BMI 1 0.05 0.0501 1.76 0.012 0.947
HLA_Time_Interaction 1 0.02 0.0157 0.55 0.004 0.991
Residuals 121 3.44 0.0285 0.824 0.555
Total 133 4.18 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.3.3 HLA type interaction with time (reference: Group3o4)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.08 0.0423 1.48 0.020 0.552
T1Dstatus 1 0.20 0.2033 7.11 0.049 0.054 .
Days 1 0.01 0.0054 0.19 0.001 0.938
seqRun 4 0.24 0.0595 2.08 0.057 0.234
Age 1 0.06 0.0643 2.25 0.015 0.409
Parity 1 0.07 0.0724 2.53 0.017 0.825
BMI 1 0.05 0.0501 1.75 0.012 0.952
HLA_Time_Interaction 1 0.00 0.0006 0.02 0.000 0.932
Residuals 121 3.46 0.0286 0.828 0.322
Total 133 4.18 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.3.4 HLA type (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
Days 1 0.01 0.0098 0.35 0.002 0.854
seqRun 4 0.21 0.0523 1.84 0.050 0.638
Age 1 0.06 0.0606 2.14 0.014 0.603
Parity 1 0.09 0.0940 3.32 0.023 0.316
BMI 1 0.11 0.1051 3.70 0.025 0.325
T1Dstatus 1 0.19 0.1889 6.66 0.045 0.046 *
HLA 2 0.05 0.0254 0.90 0.012 0.754
Residuals 122 3.46 0.0284 0.828 0.272
Total 133 4.18 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.4 Parity
11.1.9.4.1 Parity interaction with time
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.08 0.0423 1.53 0.020 0.533
T1Dstatus 1 0.20 0.2033 7.36 0.049 0.050 *
Days 1 0.01 0.0054 0.20 0.001 0.938
seqRun 4 0.24 0.0595 2.15 0.057 0.248
Age 1 0.06 0.0643 2.33 0.015 0.458
Parity 1 0.07 0.0724 2.62 0.017 0.814
BMI 1 0.05 0.0501 1.82 0.012 0.950
Parity_Time_Interaction 1 0.12 0.1190 4.31 0.028 0.043 *
Residuals 121 3.34 0.0276 0.800 0.137
Total 133 4.18 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.4.2 Parity (no interaction but within T1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.044 0.0222 0.65 0.055 0.638
T1Dstatus 1 0.010 0.0097 0.28 0.012 0.839
seqRun 1 0.067 0.0673 1.97 0.084 0.041 *
Age 1 0.029 0.0286 0.84 0.036 0.689
BMI 1 0.018 0.0179 0.52 0.022 0.778
Parity 1 0.122 0.1216 3.56 0.152 0.411
Residuals 15 0.512 0.0341 0.639 0.750
Total 22 0.801 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.4.3 Parity (no interaction but within T2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.039 0.0193 0.53 0.024 0.77
T1Dstatus 1 0.160 0.1599 4.42 0.101 0.05 *
seqRun 1 0.065 0.0652 1.80 0.041 0.92
Age 1 0.032 0.0324 0.90 0.020 0.23
BMI 1 0.012 0.0123 0.34 0.008 0.56
Parity 1 0.015 0.0153 0.42 0.010 0.92
Residuals 35 1.265 0.0362 0.796 0.53
Total 42 1.589 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.4.4 Parity (no interaction but within T3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.038 0.0192 0.80 0.022 0.561
T1Dstatus 1 0.091 0.0912 3.81 0.052 0.058 .
seqRun 1 0.003 0.0029 0.12 0.002 0.076 .
Age 1 0.014 0.0143 0.60 0.008 0.663
BMI 1 0.028 0.0280 1.17 0.016 0.875
Parity 1 0.137 0.1373 5.74 0.079 0.836
Residuals 60 1.435 0.0239 0.821 0.341
Total 67 1.747 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.5 Mode of delivery
11.1.9.5.1 Mode of delivery interaction with time (reference: Emergency caesarea)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.08 0.0423 1.48 0.020 0.549
T1Dstatus 1 0.20 0.2033 7.13 0.049 0.045 *
MOD 2 0.07 0.0366 1.28 0.018 0.615
Days 1 0.01 0.0052 0.18 0.001 0.942
seqRun 4 0.21 0.0520 1.82 0.050 0.418
Age 1 0.08 0.0821 2.88 0.020 0.220
Parity 1 0.07 0.0719 2.52 0.017 0.755
BMI 1 0.04 0.0382 1.34 0.009 0.956
MOD_Time_Interaction 1 0.02 0.0156 0.55 0.004 0.991
Residuals 119 3.40 0.0285 0.813 0.678
Total 133 4.18 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.5.2 Mode of delivery interaction with time (reference: Elective caesarea)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.08 0.0423 1.49 0.020 0.537
T1Dstatus 1 0.20 0.2033 7.17 0.049 0.057 .
MOD 2 0.07 0.0366 1.29 0.018 0.573
Days 1 0.01 0.0052 0.18 0.001 0.931
seqRun 4 0.21 0.0520 1.83 0.050 0.433
Age 1 0.08 0.0821 2.90 0.020 0.209
Parity 1 0.07 0.0719 2.54 0.017 0.736
BMI 1 0.04 0.0382 1.35 0.009 0.958
MOD_Time_Interaction 1 0.04 0.0388 1.37 0.009 0.021 *
Residuals 119 3.37 0.0283 0.807 0.391
Total 133 4.18 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.5.3 Mode of delivery interaction with time (reference: Labour)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.08 0.0423 1.49 0.020 0.573
T1Dstatus 1 0.20 0.2033 7.15 0.049 0.048 *
MOD 2 0.07 0.0366 1.29 0.018 0.615
Days 1 0.01 0.0052 0.18 0.001 0.935
seqRun 4 0.21 0.0520 1.83 0.050 0.410
Age 1 0.08 0.0821 2.89 0.020 0.219
Parity 1 0.07 0.0719 2.53 0.017 0.724
BMI 1 0.04 0.0382 1.34 0.009 0.956
MOD_Time_Interaction 1 0.03 0.0258 0.91 0.006 0.961
Residuals 119 3.39 0.0285 0.810 0.652
Total 133 4.18 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.5.4 Mode of delivery (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
Days 1 0.01 0.0098 0.34 0.002 0.854
seqRun 4 0.21 0.0523 1.84 0.050 0.629
Age 1 0.06 0.0606 2.13 0.014 0.607
Parity 1 0.09 0.0940 3.31 0.023 0.340
BMI 1 0.11 0.1051 3.70 0.025 0.324
HLA 2 0.09 0.0426 1.50 0.020 0.508
T1Dstatus 1 0.15 0.1545 5.44 0.037 0.067 .
MOD 2 0.05 0.0242 0.85 0.012 0.740
Residuals 120 3.41 0.0284 0.817 0.468
Total 133 4.18 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.5.5 Mode of delivery (no interaction: T1)
Call:
adonis(formula = D ~ SeqRun + Nulliparous + BMI_conception + T1Dstatus + Age_LMP + HLA.6DRML + MOD, data = Meta_df)
Permutation: free
Number of permutations: 999
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
SeqRun 3 0.093 0.0309 1.06 0.116 0.398
Nulliparous 1 0.194 0.1940 6.67 0.242 0.009 **
BMI_conception 1 0.010 0.0103 0.35 0.013 0.749
T1Dstatus 1 0.089 0.0887 3.05 0.111 0.060 .
Age_LMP 1 0.013 0.0132 0.45 0.016 0.647
HLA.6DRML 2 0.019 0.0096 0.33 0.024 0.879
MOD 2 0.063 0.0316 1.09 0.079 0.373
Residuals 11 0.320 0.0291 0.400
Total 22 0.801 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.5.6 Mode of delivery (no interaction: T2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
Days 1 0.054 0.0544 1.573 0.034 0.736
seqRun 3 0.247 0.0824 2.384 0.156 0.204
Age 1 0.031 0.0307 0.887 0.019 0.657
Parity 1 0.023 0.0232 0.670 0.015 0.199
BMI 1 0.060 0.0605 1.749 0.038 0.789
HLA 2 0.010 0.0051 0.147 0.006 0.966
T1Dstatus 1 0.106 0.1063 3.075 0.067 0.065 .
MOD 2 0.020 0.0098 0.283 0.012 0.876
Residuals 30 1.037 0.0346 0.653 0.751
Total 42 1.589 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.5.7 Mode of delivery (no interaction: T3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
Days 1 0.091 0.0915 3.91 0.052 0.12
seqRun 4 0.071 0.0177 0.75 0.040 0.65
Age 1 0.012 0.0125 0.53 0.007 0.62
Parity 1 0.130 0.1304 5.57 0.075 0.37
BMI 1 0.106 0.1057 4.51 0.060 0.50
HLA 2 0.018 0.0089 0.38 0.010 0.77
T1Dstatus 1 0.027 0.0267 1.14 0.015 0.28
MOD 2 0.028 0.0140 0.60 0.016 0.61
Residuals 54 1.264 0.0234 0.724 0.64
Total 67 1.747 1.000 11.1.9.6 Carbohydrate intake
11.1.9.6.1 Carbohydrate interaction with time (reference: trimester 1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.08 0.0404 1.42 0.019 0.58
T1Dstatus 1 0.19 0.1887 6.65 0.045 0.06 .
Carbs 1 0.02 0.0175 0.62 0.004 0.73
seqRun 4 0.25 0.0615 2.17 0.059 0.16
Tri 2 0.06 0.0317 1.12 0.015 0.73
Age 1 0.10 0.0967 3.41 0.023 0.14
Parity 1 0.06 0.0602 2.12 0.015 0.83
BMI 1 0.05 0.0524 1.85 0.013 0.88
Carb_Time_Interaction 1 0.02 0.0243 0.85 0.006 0.75
Residuals 117 3.32 0.0284 0.800 0.53
Total 131 4.15 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.6.2 Carbohydrate interaction with time (reference: trimester 2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.08 0.0404 1.42 0.019 0.586
T1Dstatus 1 0.19 0.1887 6.64 0.045 0.056 .
Carbs 1 0.02 0.0175 0.62 0.004 0.738
seqRun 4 0.25 0.0615 2.16 0.059 0.168
Tri 2 0.06 0.0317 1.11 0.015 0.734
Age 1 0.10 0.0967 3.40 0.023 0.149
Parity 1 0.06 0.0602 2.12 0.015 0.794
BMI 1 0.05 0.0524 1.84 0.013 0.854
Carb_Time_Interaction 1 0.02 0.0155 0.55 0.004 0.772
Residuals 117 3.33 0.0284 0.802 0.490
Total 131 4.15 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.6.3 Carbohydrate interaction with time (reference: trimester 3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.08 0.0404 1.42 0.019 0.585
T1Dstatus 1 0.19 0.1887 6.63 0.045 0.067 .
Carbs 1 0.02 0.0175 0.62 0.004 0.720
seqRun 4 0.25 0.0615 2.16 0.059 0.175
Tri 2 0.06 0.0317 1.11 0.015 0.743
Age 1 0.10 0.0967 3.40 0.023 0.131
Parity 1 0.06 0.0602 2.11 0.015 0.808
BMI 1 0.05 0.0524 1.84 0.013 0.864
Carb_Time_Interaction 1 0.01 0.0120 0.42 0.003 0.793
Residuals 117 3.33 0.0285 0.803 0.476
Total 131 4.15 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.6.4 Carbohydrate (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 0.21 0.0529 1.87 0.051 0.508
Tri 2 0.07 0.0354 1.25 0.017 0.736
Age 1 0.07 0.0678 2.39 0.016 0.647
Parity 1 0.08 0.0805 2.84 0.019 0.376
BMI 1 0.09 0.0913 3.22 0.022 0.603
HLA 2 0.08 0.0379 1.34 0.018 0.572
T1Dstatus 1 0.14 0.1435 5.06 0.035 0.073 .
Carbs 1 0.06 0.0644 2.27 0.016 0.272
Residuals 118 3.34 0.0283 0.806 0.390
Total 131 4.15 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.7 Fibre intake
11.1.9.7.1 Fibre interaction with time (reference: trimester 1)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.08 0.0404 1.40 0.019 0.601
T1Dstatus 1 0.19 0.1887 6.54 0.045 0.057 .
Fiber 1 0.01 0.0062 0.21 0.001 0.937
seqRun 4 0.23 0.0575 1.99 0.055 0.244
Tri 2 0.06 0.0297 1.03 0.014 0.761
Age 1 0.08 0.0826 2.86 0.020 0.294
Parity 1 0.07 0.0651 2.26 0.016 0.708
BMI 1 0.05 0.0463 1.60 0.011 0.913
Fiber_Time_Interaction 1 0.01 0.0142 0.49 0.003 0.514
Residuals 117 3.38 0.0289 0.814 0.554
Total 131 4.15 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.7.2 Fibre interaction with time (reference: trimester 2)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.08 0.0404 1.39 0.019 0.580
T1Dstatus 1 0.19 0.1887 6.52 0.045 0.061 .
Fiber 1 0.01 0.0062 0.21 0.001 0.926
seqRun 4 0.23 0.0575 1.99 0.055 0.259
Tri 2 0.06 0.0297 1.02 0.014 0.759
Age 1 0.08 0.0826 2.85 0.020 0.298
Parity 1 0.07 0.0651 2.25 0.016 0.726
BMI 1 0.05 0.0463 1.60 0.011 0.917
Fiber_Time_Interaction 1 0.00 0.0042 0.14 0.001 0.749
Residuals 117 3.39 0.0289 0.816 0.592
Total 131 4.15 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.7.3 Fibre interaction with time (reference: trimester 3)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.08 0.0404 1.40 0.019 0.561
T1Dstatus 1 0.19 0.1887 6.54 0.045 0.053 .
Fiber 1 0.01 0.0062 0.21 0.001 0.914
seqRun 4 0.23 0.0575 1.99 0.055 0.264
Tri 2 0.06 0.0297 1.03 0.014 0.791
Age 1 0.08 0.0826 2.86 0.020 0.265
Parity 1 0.07 0.0651 2.26 0.016 0.717
BMI 1 0.05 0.0463 1.60 0.011 0.920
Fiber_Time_Interaction 1 0.01 0.0116 0.40 0.003 0.531
Residuals 117 3.38 0.0289 0.814 0.552
Total 131 4.15 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.7.4 Fibre (no interaction)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 0.21 0.0529 1.84 0.051 0.495
Tri 2 0.07 0.0354 1.23 0.017 0.748
Age 1 0.07 0.0678 2.36 0.016 0.680
Parity 1 0.08 0.0805 2.80 0.019 0.373
BMI 1 0.09 0.0913 3.18 0.022 0.611
HLA 2 0.08 0.0379 1.32 0.018 0.562
T1Dstatus 1 0.14 0.1435 4.99 0.035 0.079 .
Fiber 1 0.02 0.0176 0.61 0.004 0.664
Residuals 118 3.39 0.0287 0.817 0.525
Total 131 4.15 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.8 1,5-AG (glucose control measurement)
11.1.9.8.1 1,5-AG interaction with time
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.12 0.0583 2.09 0.033 0.452
T1Dstatus 1 0.24 0.2400 8.61 0.067 0.036 *
Days 1 0.01 0.0086 0.31 0.002 0.894
seqRun 3 0.14 0.0468 1.68 0.039 0.600
Age 1 0.10 0.0994 3.57 0.028 0.115
Parity 1 0.04 0.0434 1.56 0.012 0.895
BMI 1 0.01 0.0132 0.48 0.004 0.984
AG15 1 0.09 0.0850 3.05 0.024 0.007 **
AG15_T1D_Interaction 1 0.04 0.0356 1.28 0.010 0.861
Residuals 100 2.79 0.0279 0.781 0.170
Total 112 3.57 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.8.2 1,5-AG within T1D women
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.018 0.0090 0.59 0.019 0.911
Days 1 0.046 0.0457 3.00 0.049 0.055 .
seqRun 3 0.124 0.0414 2.72 0.133 0.352
Age 1 0.014 0.0139 0.91 0.015 0.258
Parity 1 0.066 0.0660 4.33 0.071 0.458
BMI 1 0.027 0.0270 1.77 0.029 0.279
AG15 1 0.041 0.0413 2.71 0.044 0.023 *
Residuals 39 0.594 0.0152 0.639 0.198
Total 49 0.930 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 111.1.9.8.3 1,5-AG interaction with time (within non-T1D women)
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.156 0.0779 2.18 0.066 0.394
Days 1 0.011 0.0112 0.31 0.005 0.728
seqRun 3 0.084 0.0282 0.79 0.036 0.905
Age 1 0.145 0.1454 4.07 0.062 0.063 .
Parity 1 0.018 0.0177 0.50 0.007 0.957
BMI 1 0.010 0.0100 0.28 0.004 0.647
AG15 1 0.079 0.0788 2.21 0.033 0.840
Residuals 52 1.859 0.0358 0.787 0.734
Total 62 2.363 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 112 Functional analysis (Pathways)
In order to functionally annotate the metagenomic data, we used Kraken2 to filter out human genes more stringently before running HUMAnN2 again. For each sample, the HUMAnN2 output contained the following files:
XX_pathcoverage.tsv: This file details the abundance of each pathway in the community as a function of the abundances of the pathway's component reactions, with each reaction's abundance computed as the sum over abundances of genes catalyzing the reaction. Pathways with zero abundance are not included in the file. Pathway abundance is proportional to the number of complete "copies" of the pathway in the community (from the HUMAnN2 manual).
XX_genefamilies.tsv: This file details the abundance of each gene family in the community. Gene families are groups of evolutionarily-related protein-coding sequences that often perform similar functions. Gene family abundance at the community level is stratified to show the contributions from known and unknown species. Individual species' abundance contributions sum to the community total abundance (from the HUMAnN2 manual).
- The genefamilies.csv file can contain a very large number of features depending on the complexity of your underlying sample. In order to simplify the exploration of gene family abundance data, users can regroup gene families into other functional categories (from the HUMAnN2 manual). Therefore, we regrouped our resulting gene families into MetaCyc reactions and Kegg Orthology (KO) functional categories, which has to be done in a per sample manner. Example:
- humann2_regroup_table --input NGU5366A1_genefamilies.tsv --groups uniref90_ko --output ./NGU5366A1_genefamilies_Regrouped_KO.tsv
- HUMAnN2 quantifies genes and pathways in units of RPKs (reads per kilobase). These account for gene length but not sample sequencing depth. Therefore, a user will renormalize their samples prior to downstream analysis to relative abundance or copies per million (CPM) units. Both of these represent "total sum scaling (TSS)"-style normalization: in the former case, each sample is constrained to sum to 1, whereas in the latter case (CPMs) samples are constrained to sum to 1 million. Units out of 1 million are often more convenient for tables with many, many features (such as genefamilies.tsv tables). CPM as used here does not refer to unnormalized COUNTS per million, but rather copies per million. CPMs as used here are a generic analog of the TPM (transcript per million) unit in RNA-seq. You may wish to use the abbreviation CoPM for added clarity. (from the HUMAnN2 manual). We normilized the counts for each sample file for their three functional tables (XX_genefamilies.tsv, XX_genefamilies_Regrouped_KO.tsv and XX_genefamilies_Regrouped_MetaCyc.tsv) to CoPM. Example:
- humann2_renorm_table --input NGU5366A1_genefamilies_Regrouped_KO.tsv --output NGU5366A1_genefamilies_Regrouped_KO_CoPM.tsv --units cpm
- Each normalized file, contained one sample. Therefore, in order to obtain a table with the functional profiles for all the samples, we need to join them into one. Example:
- humann2_join_tables --input KO --output Pregnancy_genefamilies_KO_Rel.tsv --file_name Complete_genefamilies_Regrouped_KO_Rel.tsv
- The functional profiles are stratified, which means that the sum of the species abundance of a given gene gives the abundance of the gene at the community level. The stratification shows the contributions from known and unknown species to a given function. If we are interested in knowing if there is a significant difference in the abundance of a specific function at the community level (i.e. irrespective of which species is contributing to it), the abundances need to be unstratified prior to the analysis. This is done as in the following exmaple:
- humann2_split_stratified_table --input Complete_genefamilies_Regrouped_KO_Rel.tsv --output Split/
The folder split will contain stratified and unstratified abundances.
Note: Scripts used for regrouping, normalization, joinning tables and stratification are part of HUMAnN2.
The resulting files for pathways, metacyc reactions and Kegg orthology (KO) gene categories were imported into R to process with the Phyloseq (https://github.com/joey711/phyloseq) and other packages. The analysis performed in R is described in this document.
12.1 Bar plots taxonomy
12.2 Functional Alpha diversity (Days)
Call:
geeglm(formula = Observed ~ t1dfactor * days_c + age_c + nullip +
bmi_c + HLA + SeqRun, data = DivCal_R_df, id = motherid,
corstr = "exchangeable")
Coefficients:
Estimate Std.err Wald Pr(>|W|)
(Intercept) 270.37171 8.69441 967.04 < 2e-16 ***
t1dfactorT1D 21.79016 6.07686 12.86 0.00034 ***
days_c 0.03589 0.06653 0.29 0.58952
age_c 0.67547 0.79963 0.71 0.39826
nullipYes -16.71466 6.44698 6.72 0.00952 **
bmi_c 0.23971 0.69683 0.12 0.73085
HLADRXX 15.41744 9.07571 2.89 0.08936 .
HLAGroup3o4 13.17415 8.22482 2.57 0.10921
SeqRun2 -1.79192 9.20810 0.04 0.84570
SeqRun3 3.39900 8.12048 0.18 0.67553
SeqRun4 15.49328 8.29136 3.49 0.06168 .
SeqRun6 -3.62746 8.39669 0.19 0.66573
t1dfactorT1D:days_c -0.00592 0.09783 0.00 0.95178
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
Correlation structure = exchangeable
Estimated Scale Parameters:
Estimate Std.err
(Intercept) 1096 132
Link = identity
Estimated Correlation Parameters:
Estimate Std.err
alpha 0.0827 0.199
Number of clusters: 121 Maximum cluster size: 3 
12.3 Functional Alpha diversity (Trimesters)
Call:
geeglm(formula = Observed ~ t1dfactor * Tri + age_c + nullip +
bmi_c + HLA + SeqRun, data = DivCal_R_df, id = motherid,
corstr = "exchangeable")
Coefficients:
Estimate Std.err Wald Pr(>|W|)
(Intercept) 259.491 12.474 432.76 <2e-16 ***
t1dfactorT1D 30.426 16.236 3.51 0.0609 .
TriT2 17.406 11.315 2.37 0.1240
TriT3 9.483 11.851 0.64 0.4236
age_c 0.806 0.786 1.05 0.3055
nullipYes -16.770 6.377 6.92 0.0085 **
bmi_c 0.169 0.726 0.05 0.8159
HLADRXX 15.914 9.109 3.05 0.0806 .
HLAGroup3o4 14.645 8.301 3.11 0.0777 .
SeqRun2 1.314 8.441 0.02 0.8763
SeqRun3 2.710 7.970 0.12 0.7338
SeqRun4 14.999 8.025 3.49 0.0616 .
SeqRun6 -4.398 8.293 0.28 0.5959
t1dfactorT1D:TriT2 -16.864 18.267 0.85 0.3559
t1dfactorT1D:TriT3 -5.873 17.982 0.11 0.7439
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
Correlation structure = exchangeable
Estimated Scale Parameters:
Estimate Std.err
(Intercept) 1082 131
Link = identity
Estimated Correlation Parameters:
Estimate Std.err
alpha 0.0646 0.208
Number of clusters: 121 Maximum cluster size: 3 12.4 Alpha diversity (T1D vs. non-T1D categorical time [Trimester])
12.5 Beta diversity analysis
12.5.1 Interaction between T1D status and Time
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 0.077 0.0193 1.33 0.037 0.904
Days 1 0.015 0.0148 1.02 0.007 0.743
T1D_Time_Interaction 1 0.041 0.0406 2.79 0.019 0.021 *
Age 1 0.041 0.0406 2.79 0.019 0.530
Parity 1 0.036 0.0360 2.48 0.017 0.344
BMI 1 0.027 0.0268 1.85 0.013 0.997
HLA 2 0.074 0.0371 2.56 0.035 0.149
T1Dstatus 1 0.028 0.0284 1.95 0.014 0.388
Residuals 121 1.757 0.0145 0.838 0.254
Total 133 2.096 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1[1] 0.021
12.5.2 T1D status in trimester 1
Call:
adonis(formula = D ~ SeqRun + Nulliparous + Age_LMP + BMI_conception + HLA.6DRML + T1Dstatus, data = Meta_dfTri)
Permutation: free
Number of permutations: 999
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
SeqRun 3 0.037 0.0124 0.742 0.096 0.808
Nulliparous 1 0.029 0.0288 1.715 0.074 0.079 .
Age_LMP 1 0.021 0.0211 1.256 0.054 0.212
BMI_conception 1 0.013 0.0130 0.775 0.033 0.627
HLA.6DRML 2 0.039 0.0195 1.164 0.100 0.253
T1Dstatus 1 0.033 0.0333 1.984 0.085 0.062 .
Residuals 13 0.218 0.0168 0.558
Total 22 0.391 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1[1] 0.062Beta diversity Plot
12.5.3 T1D status in trimester 2
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 3 0.063 0.0211 1.518 0.101 0.57
Age 1 0.019 0.0194 1.399 0.031 0.60
Parity 1 0.014 0.0143 1.032 0.023 0.24
BMI 1 0.014 0.0138 0.989 0.022 0.95
HLA 2 0.033 0.0164 1.183 0.052 0.62
T1Dstatus 1 0.027 0.0273 1.962 0.043 0.10
Residuals 33 0.459 0.0139 0.728 0.30
Total 42 0.630 1.000 Beta diversity Plot
12.5.4 T1D status in trimester 3
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 0.050 0.0124 0.809 0.047 0.502
Age 1 0.016 0.0162 1.051 0.015 0.369
Parity 1 0.028 0.0278 1.811 0.026 0.369
BMI 1 0.023 0.0228 1.484 0.022 0.762
HLA 2 0.036 0.0180 1.173 0.034 0.325
T1Dstatus 1 0.025 0.0254 1.653 0.024 0.094 .
Residuals 57 0.877 0.0154 0.831 0.306
Total 67 1.055 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
12.5.5 Days within T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.055 0.0275 2.05 0.050 0.495
seqRun 3 0.092 0.0306 2.28 0.084 0.249
Age 1 0.028 0.0279 2.08 0.025 0.921
Parity 1 0.094 0.0944 7.04 0.086 0.083 .
BMI 1 0.038 0.0377 2.81 0.034 0.505
Days 1 0.013 0.0127 0.95 0.012 0.234
Residuals 58 0.777 0.0134 0.709 0.181
Total 67 1.096 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
12.5.6 Trimester within T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.055 0.0275 2.03 0.050 0.483
seqRun 3 0.092 0.0306 2.27 0.084 0.271
Age 1 0.028 0.0279 2.07 0.025 0.900
Parity 1 0.094 0.0944 6.99 0.086 0.072 .
BMI 1 0.038 0.0377 2.79 0.034 0.523
Tri 2 0.021 0.0103 0.76 0.019 0.443
Residuals 57 0.769 0.0135 0.702 0.211
Total 67 1.096 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
12.5.7 Days within non-T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.063 0.0315 2.292 0.066 0.251
seqRun 4 0.052 0.0130 0.946 0.055 0.998
Age 1 0.043 0.0434 3.157 0.045 0.014 *
Parity 1 0.018 0.0176 1.279 0.018 0.944
BMI 1 0.010 0.0102 0.740 0.011 0.871
Days 1 0.012 0.0116 0.842 0.012 0.701
Residuals 55 0.756 0.0138 0.793 0.613
Total 65 0.954 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
12.5.8 Trimester within non-T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.063 0.0315 2.262 0.066 0.257
seqRun 4 0.052 0.0130 0.934 0.055 1.000
Age 1 0.043 0.0434 3.117 0.045 0.011 *
Parity 1 0.018 0.0176 1.263 0.018 0.945
BMI 1 0.010 0.0102 0.731 0.011 0.869
Tri 2 0.016 0.0079 0.565 0.016 0.955
Residuals 54 0.752 0.0139 0.788 0.787
Total 65 0.954 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
13 Functional analysis (Kegg Orthology)
13.1 Bar plots taxonomy
13.2 Functional Alpha diversity (Days)
Call:
geeglm(formula = Observed ~ t1dfactor * days_c + age_c + nullip +
bmi_c + HLA + SeqRun, data = DivCal_R_df, id = motherid,
corstr = "exchangeable")
Coefficients:
Estimate Std.err Wald Pr(>|W|)
(Intercept) 3200.574 121.672 691.94 <2e-16 ***
t1dfactorT1D 219.495 86.247 6.48 0.0109 *
days_c 0.274 0.848 0.10 0.7465
age_c 7.818 11.420 0.47 0.4936
nullipYes -261.839 90.461 8.38 0.0038 **
bmi_c -0.968 9.683 0.01 0.9203
HLADRXX 69.320 123.799 0.31 0.5755
HLAGroup3o4 115.169 115.933 0.99 0.3205
SeqRun2 185.229 117.657 2.48 0.1154
SeqRun3 9.051 111.436 0.01 0.9353
SeqRun4 159.762 115.219 1.92 0.1656
SeqRun6 -89.142 123.508 0.52 0.4704
t1dfactorT1D:days_c -0.199 1.331 0.02 0.8810
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
Correlation structure = exchangeable
Estimated Scale Parameters:
Estimate Std.err
(Intercept) 209774 24094
Link = identity
Estimated Correlation Parameters:
Estimate Std.err
alpha 0.149 0.203
Number of clusters: 121 Maximum cluster size: 3 
13.3 Functional Alpha diversity (Trimesters)
Call:
geeglm(formula = Observed ~ t1dfactor * Tri + age_c + nullip +
bmi_c + HLA + SeqRun, data = DivCal_R_df, id = motherid,
corstr = "exchangeable")
Coefficients:
Estimate Std.err Wald Pr(>|W|)
(Intercept) 3109.43 174.67 316.90 <2e-16 ***
t1dfactorT1D 297.46 220.68 1.82 0.1777
TriT2 170.29 156.08 1.19 0.2753
TriT3 65.86 156.99 0.18 0.6749
age_c 9.14 11.22 0.66 0.4154
nullipYes -263.11 89.64 8.62 0.0033 **
bmi_c -1.78 10.03 0.03 0.8593
HLADRXX 72.70 124.59 0.34 0.5595
HLAGroup3o4 129.58 116.47 1.24 0.2659
SeqRun2 220.43 109.43 4.06 0.0440 *
SeqRun3 1.41 110.02 0.00 0.9898
SeqRun4 152.01 112.79 1.82 0.1778
SeqRun6 -96.81 121.95 0.63 0.4273
t1dfactorT1D:TriT2 -147.61 252.06 0.34 0.5581
t1dfactorT1D:TriT3 -53.76 242.41 0.05 0.8245
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
Correlation structure = exchangeable
Estimated Scale Parameters:
Estimate Std.err
(Intercept) 207892 24295
Link = identity
Estimated Correlation Parameters:
Estimate Std.err
alpha 0.129 0.201
Number of clusters: 121 Maximum cluster size: 3 13.4 Beta diversity analysis
13.4.1 Interaction between T1D status and Time
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 0.19 0.0480 1.94 0.052 0.260
Days 1 0.05 0.0511 2.07 0.014 0.087 .
T1D_Time_Interaction 1 0.13 0.1288 5.22 0.035 0.034 *
Age 1 0.09 0.0855 3.46 0.023 0.827
Parity 1 0.05 0.0493 1.99 0.013 0.073 .
BMI 1 0.06 0.0603 2.44 0.016 0.994
HLA 2 0.10 0.0507 2.05 0.027 0.340
T1Dstatus 1 0.04 0.0378 1.53 0.010 0.674
Residuals 121 2.99 0.0247 0.809 0.217
Total 133 3.69 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1[1] 0.034
13.4.2 T1D status in trimester 1
Call:
adonis(formula = D ~ SeqRun + Nulliparous + Age_LMP + BMI_conception + HLA.6DRML + T1Dstatus, data = Meta_dfTri)
Permutation: free
Number of permutations: 999
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
SeqRun 3 0.070 0.0234 0.783 0.103 0.760
Nulliparous 1 0.044 0.0440 1.474 0.065 0.139
Age_LMP 1 0.034 0.0343 1.149 0.050 0.278
BMI_conception 1 0.021 0.0207 0.693 0.030 0.756
HLA.6DRML 2 0.056 0.0281 0.942 0.083 0.501
T1Dstatus 1 0.066 0.0660 2.212 0.097 0.022 *
Residuals 13 0.388 0.0298 0.571
Total 22 0.679 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1[1] 0.022Beta diversity Plot
13.4.3 T1D status in trimester 2
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 3 0.130 0.0434 1.83 0.116 0.001 ***
Age 1 0.031 0.0314 1.32 0.028 0.509
Parity 1 0.033 0.0334 1.41 0.030 0.001 ***
BMI 1 0.027 0.0275 1.16 0.025 0.505
HLA 2 0.060 0.0299 1.26 0.053 0.467
T1Dstatus 1 0.055 0.0548 2.31 0.049 0.062 .
Residuals 33 0.782 0.0237 0.699 0.156
Total 42 1.119 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
13.4.4 T1D status in trimester 3
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 0.125 0.0311 1.216 0.068 0.502
Age 1 0.041 0.0408 1.593 0.022 0.374
Parity 1 0.031 0.0315 1.229 0.017 0.001 ***
BMI 1 0.062 0.0619 2.416 0.034 0.502
HLA 2 0.045 0.0223 0.869 0.024 0.742
T1Dstatus 1 0.055 0.0553 2.159 0.030 0.026 *
Residuals 57 1.460 0.0256 0.803 0.181
Total 67 1.818 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
13.4.5 Days within T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.095 0.0477 2.09 0.052 0.430
seqRun 3 0.170 0.0565 2.48 0.093 0.287
Age 1 0.042 0.0418 1.83 0.023 0.954
Parity 1 0.086 0.0859 3.77 0.047 0.319
BMI 1 0.080 0.0798 3.50 0.044 0.421
Days 1 0.032 0.0321 1.41 0.018 0.087 .
Residuals 58 1.321 0.0228 0.724 0.339
Total 67 1.825 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
13.4.6 Trimester within T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.095 0.0477 2.08 0.052 0.45
seqRun 3 0.170 0.0565 2.47 0.093 0.26
Age 1 0.042 0.0418 1.83 0.023 0.95
Parity 1 0.086 0.0859 3.75 0.047 0.30
BMI 1 0.080 0.0798 3.49 0.044 0.41
Tri 2 0.049 0.0246 1.08 0.027 0.12
Residuals 57 1.304 0.0229 0.714 0.33
Total 67 1.825 1.000 Beta diversity Plot
13.4.7 Days within non-T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.126 0.0629 2.65 0.073 0.186
seqRun 4 0.127 0.0317 1.34 0.073 0.961
Age 1 0.102 0.1024 4.32 0.059 0.014 *
Parity 1 0.020 0.0197 0.83 0.011 0.985
BMI 1 0.019 0.0193 0.81 0.011 0.702
Days 1 0.029 0.0289 1.22 0.017 0.438
Residuals 55 1.303 0.0237 0.755 0.210
Total 65 1.726 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
13.4.8 Trimester within non-T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.126 0.0629 2.63 0.073 0.218
seqRun 4 0.127 0.0317 1.33 0.073 0.970
Age 1 0.102 0.1024 4.29 0.059 0.011 *
Parity 1 0.020 0.0197 0.83 0.011 0.976
BMI 1 0.019 0.0193 0.81 0.011 0.721
Tri 2 0.043 0.0213 0.89 0.025 0.847
Residuals 54 1.289 0.0239 0.747 0.372
Total 65 1.726 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
14 Functional analysis (MetaCyc reactions)
14.1 Bar plots taxonomy
14.2 Functional Alpha diversity (Days)
Call:
geeglm(formula = Observed ~ t1dfactor * days_c + age_c + nullip +
bmi_c + HLA + SeqRun, data = DivCal_R_df, id = motherid,
corstr = "exchangeable")
Coefficients:
Estimate Std.err Wald Pr(>|W|)
(Intercept) 2004.5197 46.2156 1881.24 < 2e-16 ***
t1dfactorT1D 105.8145 32.0574 10.90 0.00096 ***
days_c 0.1934 0.3213 0.36 0.54726
age_c 2.3352 4.0931 0.33 0.56832
nullipYes -83.7932 34.0845 6.04 0.01396 *
bmi_c -0.0288 3.5634 0.00 0.99354
HLADRXX 43.0525 45.9961 0.88 0.34927
HLAGroup3o4 60.5172 42.0367 2.07 0.14997
SeqRun2 28.8027 45.5925 0.40 0.52755
SeqRun3 24.6452 41.1787 0.36 0.54951
SeqRun4 75.2434 42.4728 3.14 0.07647 .
SeqRun6 -34.6553 45.9168 0.57 0.45040
t1dfactorT1D:days_c -0.2802 0.5178 0.29 0.58846
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
Correlation structure = exchangeable
Estimated Scale Parameters:
Estimate Std.err
(Intercept) 28904 4037
Link = identity
Estimated Correlation Parameters:
Estimate Std.err
alpha 0.0329 0.222
Number of clusters: 121 Maximum cluster size: 3 
14.3 Functional Alpha diversity (Trimesters)
Call:
geeglm(formula = Observed ~ t1dfactor * Tri + age_c + nullip +
bmi_c + HLA + SeqRun, data = DivCal_R_df, id = motherid,
corstr = "exchangeable")
Coefficients:
Estimate Std.err Wald Pr(>|W|)
(Intercept) 1948.280 65.637 881.06 <2e-16 ***
t1dfactorT1D 168.710 87.379 3.73 0.054 .
TriT2 92.654 59.743 2.41 0.121
TriT3 50.426 59.210 0.73 0.394
age_c 2.992 3.993 0.56 0.454
nullipYes -84.967 33.584 6.40 0.011 *
bmi_c -0.517 3.730 0.02 0.890
HLADRXX 43.247 46.673 0.86 0.354
HLAGroup3o4 66.236 42.588 2.42 0.120
SeqRun2 46.402 41.861 1.23 0.268
SeqRun3 22.509 40.371 0.31 0.577
SeqRun4 73.316 40.851 3.22 0.073 .
SeqRun6 -38.003 45.246 0.71 0.401
t1dfactorT1D:TriT2 -92.463 98.478 0.88 0.348
t1dfactorT1D:TriT3 -61.983 95.940 0.42 0.518
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
Correlation structure = exchangeable
Estimated Scale Parameters:
Estimate Std.err
(Intercept) 28520 4103
Link = identity
Estimated Correlation Parameters:
Estimate Std.err
alpha 0.000515 0.221
Number of clusters: 121 Maximum cluster size: 3 14.4 Beta diversity analysis
14.4.1 Interaction between T1D status and Time
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 0.088 0.0221 1.55 0.044 0.748
Days 1 0.020 0.0200 1.40 0.010 0.295
T1D_Time_Interaction 1 0.040 0.0405 2.84 0.020 0.065 .
Age 1 0.040 0.0403 2.83 0.020 0.830
Parity 1 0.030 0.0300 2.10 0.015 0.463
BMI 1 0.027 0.0273 1.91 0.013 0.989
HLA 2 0.043 0.0213 1.49 0.021 0.660
T1Dstatus 1 0.016 0.0157 1.10 0.008 0.804
Residuals 121 1.727 0.0143 0.850 0.880
Total 133 2.032 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1[1] 0.065
14.4.2 T1D status in trimester 1
Call:
adonis(formula = D ~ SeqRun + Nulliparous + Age_LMP + BMI_conception + HLA.6DRML + T1Dstatus, data = Meta_dfTri)
Permutation: free
Number of permutations: 999
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
SeqRun 3 0.030 0.0100 0.650 0.092 0.90
Nulliparous 1 0.022 0.0221 1.439 0.068 0.15
Age_LMP 1 0.010 0.0101 0.658 0.031 0.76
BMI_conception 1 0.021 0.0213 1.383 0.065 0.18
HLA.6DRML 2 0.022 0.0110 0.717 0.067 0.79
T1Dstatus 1 0.021 0.0212 1.377 0.065 0.21
Residuals 13 0.200 0.0154 0.612
Total 22 0.327 1.000 [1] 0.207Beta diversity Plot
14.4.3 T1D status in trimester 2
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 3 0.080 0.0267 1.953 0.128 0.96
Age 1 0.021 0.0213 1.555 0.034 0.66
Parity 1 0.012 0.0123 0.895 0.020 0.51
BMI 1 0.012 0.0124 0.906 0.020 0.65
HLA 2 0.024 0.0118 0.861 0.038 0.82
T1Dstatus 1 0.023 0.0231 1.686 0.037 0.17
Residuals 33 0.452 0.0137 0.723 0.57
Total 42 0.625 1.000 Beta diversity Plot
14.4.4 T1D status in trimester 3
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
seqRun 4 0.041 0.0102 0.637 0.038 0.51
Age 1 0.020 0.0204 1.278 0.019 0.36
Parity 1 0.029 0.0285 1.786 0.027 0.51
BMI 1 0.018 0.0181 1.137 0.017 0.73
HLA 2 0.023 0.0116 0.726 0.022 0.81
T1Dstatus 1 0.017 0.0171 1.069 0.016 0.35
Residuals 57 0.910 0.0160 0.860 0.87
Total 67 1.058 1.000 Beta diversity Plot
14.4.5 Days within T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.034 0.0172 1.49 0.037 0.807
seqRun 3 0.087 0.0289 2.49 0.094 0.309
Age 1 0.024 0.0238 2.05 0.026 0.611
Parity 1 0.060 0.0603 5.20 0.065 0.055 .
BMI 1 0.040 0.0401 3.46 0.043 0.499
Days 1 0.009 0.0089 0.76 0.010 0.438
Residuals 58 0.672 0.0116 0.726 0.414
Total 67 0.926 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
14.4.6 Trimester within T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.034 0.0172 1.47 0.037 0.790
seqRun 3 0.087 0.0289 2.47 0.094 0.287
Age 1 0.024 0.0238 2.03 0.026 0.635
Parity 1 0.060 0.0603 5.15 0.065 0.076 .
BMI 1 0.040 0.0401 3.42 0.043 0.527
Tri 2 0.014 0.0070 0.60 0.015 0.678
Residuals 57 0.667 0.0117 0.720 0.466
Total 67 0.926 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
14.4.7 Days within non-T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.070 0.0348 2.256 0.066 0.284
seqRun 4 0.050 0.0125 0.813 0.047 0.999
Age 1 0.045 0.0455 2.948 0.043 0.018 *
Parity 1 0.017 0.0173 1.122 0.016 0.919
BMI 1 0.015 0.0149 0.965 0.014 0.128
Days 1 0.012 0.0124 0.803 0.012 0.515
Residuals 55 0.848 0.0154 0.802 0.619
Total 65 1.058 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
14.4.8 Trimester within non-T1D
Call:
adonis(formula = D ~ ., data = mtdat[, metadata_order, drop = F], permutations = 0)
Permutation: free
Number of permutations: 0
Terms added sequentially (first to last)
Df SumsOfSqs MeanSqs F.Model R2 Pr(>F)
HLA 2 0.070 0.0348 2.225 0.066 0.27
seqRun 4 0.050 0.0125 0.802 0.047 1.00
Age 1 0.045 0.0455 2.906 0.043 0.02 *
Parity 1 0.017 0.0173 1.106 0.016 0.93
BMI 1 0.015 0.0149 0.952 0.014 0.13
Tri 2 0.016 0.0080 0.511 0.015 0.93
Residuals 54 0.845 0.0156 0.798 0.75
Total 65 1.058 1.000
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1Beta diversity Plot
